KR101490003B1 - Pyrrolidine derivatives - Google Patents

Abstract

The present invention relates to a compound of formula (I) or a pharmaceutically active salt thereof. The compounds of the present invention have been found to be highly potent NK-3 receptor antagonists for the treatment of depression, pain, psychosis, Parkinson's disease, schizophrenia, anxiety and attention deficit hyperactivity disorder (ADHD).
(I)

Description

PYRROLIDINE DERIVATIVES < RTI ID = 0.0 >

The present invention relates to compounds of formula (I)

(I)

In this formula,

R ¹ is hydrogen, halogen, cyano, lower alkyl, or lower alkyl substituted by halogen; n is 1, 2 or 3, provided that when n is 2 or 3, R < ¹ > can be different;

R ² is hydrogen or methyl;

R ³ is (CH ₂ ) _r C (O) NH ₂ or (CH ₂ ) _r -CN where r is 1 or 2, or

의 비-방향족 헤테로사이클릭 기이고, 여기서The

Aromatic heterocyclic group of formula < RTI ID = 0.0 >

X is N or CH;

Y is ^{-C (R) (R 7)} -, -N (R 7 ') -, -S (O) 2 or O;

R <^6> is hydrogen, di-lower alkyl or = O;

o and m are independently of each other 0, 1 or 2;

p is 0, 1 or 2;

R is hydrogen, halogen or lower alkyl;

R ⁷ is hydrogen, halogen, hydroxy, lower alkyl substituted by hydroxy, cyano, or lower alkoxy;

R ^{7 '} Hydrogen, -C (O) - lower alkyl, -C (O) O- lower alkyl, -C (O) CH ₂ O- lower _{alkyl, -C (O) CH 2 CN} , or

-C (O) - cycloalkyl, cycloalkyl, or -CH ₂ - cycloalkyl (wherein the cycloalkyl group is optionally halogen, lower alkoxy, lower alkyl substituted by halogen, cyano, -CH ₂ O- lower alkyl, or Lower alkyl), or

-C (O) -heterocycloalkyl or heterocycloalkyl, or

Lower alkoxy, lower alkyl substituted by halogen, C (O) NH-lower alkyl, -C (O) -lower alkyl, _{C (O) NH 2, C} (O) - lower alkyl, S (O) ₂ - lower alkyl or cyano-substituted, and the furnace;

Z is -O-, -NH- or -N (lower alkyl) -;

R ⁴ is lower alkyl, by lower alkyl, cycloalkyl substituted by lower alkyl, hydroxy substituted lower alkyl substituted by halogen, (CH _{2) 2,3} -O- lower _{alkyl, CH (CH 3) CH 2} - O- lower alkyl, (CH _{2) q} CN, bicyclo [2.2.1] heptane-yl, or

Optionally substituted by lower alkyl, lower alkyl, lower alkoxy or halogen-substituted by halogen, (CH _{2) q} - cycloalkyl, or

(CH ₂ ) _q -heterocycloalkyl, (CH ₂ ) _q -aryl, CH (lower alkyl) -aryl, CH (cycloalkyl) -aryl or (CH ₂ ) _q -heteroaryl, , The aryl or heteroaryl ring is optionally substituted with halogen, hydroxy, lower alkyl, lower alkyl substituted by halogen, S (O) ₂ -lower alkyl, cyano or lower alkoxy;

q is 0, 1 or 2;

The present invention includes all stereoisomeric and enantiomeric forms of the compounds of formula I as well as all stereoisomeric forms thereof, including racemic and non-racemic mixtures thereof.

The compounds of the present invention have been found to be highly potent NK-3 receptor antagonists for the treatment of depression, pain, psychosis, Parkinson's disease, schizophrenia, anxiety and attention deficit hyperactivity disorder (ADHD).

Three main mammalian tachykinins substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) is Phe-X-Gly-Leu- Met-NH ₂ common COOH- terminal pentapeptide sequence Lt; / RTI &gt; As neurotransmitters, these peptides exert their biological activity through three distinct neurokinin (NK) receptors, referred to as NK-1, NK-2 and NK-3. SP binds preferentially to the NK-1 receptor, NKA to the NK-2 receptor, and NKB to the NK-3 receptor.

The NK-3 receptor is characterized by dominant expression in the CNS and is involved in the regulation of the central monoamnionic system. Because of these properties, the NK-3 receptor is a potential target for central nervous system disorders such as anxiety, depression, bipolar disorder, Parkinson's disease, schizophrenia and pain (Neurosci. Letters, 2000, 283, 185-188; Exp Neuroscience, 1996, 74, 403-414; Neuropeptides, 1998, 32, 481-488).

Schizophrenia is one of the major neuropsychiatric disorders characterized by severe chronic mental impairment. About 1% of the world's population suffers from these devastating diseases. Symptoms start in early adulthood, followed by periods of interpersonal and social functioning. Schizophrenia manifests as hallucinations, hallucinations, paranoia, delusions (benign symptoms), slowed mood, depression, anesthesia, linguistic deficit, memory and attention deficit, and social atrophy (negative symptoms).

For decades scientists and clinicians have sought to develop ideal drugs for the pharmacological treatment of schizophrenia. However, the complexity of the disorder resulting from a wide range of symptoms has hindered scientists and clinicians' efforts. There are no specific lesions for the diagnosis of schizophrenia and there is no single symptom that is consistently present in all patients. As a result, the diagnosis of schizophrenia as a single disorder or a variety of different disorders has been discussed but not yet clarified. The main difficulty in the development of new drugs for schizophrenia is the lack of knowledge of the causes and nature of these diseases. Several neurological assumptions, such as dopamine, serotonin and glutamate hypothesis, have been proposed based on pharmacological studies to theoretically explain the development of corresponding therapies. However, given the complexity of schizophrenia, a suitable multiple receptor affinity profile may be required for efficacy for positive and negative symptoms and symptoms. In addition, the ideal drug for schizophrenia will preferably have a low dosage which allows for once-a-day administration due to the low adhesion of schizophrenic patients.

Recently, clinical studies on selective NK1 and NK2 receptor antagonists have been presented in the literature that provide results for treatment of vomiting, depression, anxiety, pain and migraine (NK1) and asthma (NK2 and NK1). The most interesting data was provided in the treatment with chemotherapy-induced vomiting, nausea and depression with NK1-receptor antagonists and with asthmatic NK2-receptor antagonists. In contrast, no clinical data on NK3 receptor antagonists appeared in the literature until 2000. Osanetant (SR 142,801) from Sanofi-Synthelabo is the first identified potent and selective non-peptide antagonist described for the NK3 tachykinin receptor for potential treatment of schizophrenia Reported in Current Opinion in Investigational Drugs, 2001, 2 (7), 950-956 and Psychiatric Disorders Study 4, Schizophrenia, June 2003, Decision Recources, Inc., Waltham, Massachusetts. The proposed drug SR142,801 appeared active in the clinical phase II trials for positive symptoms of schizophrenia, such as altered behavior, delusions, hallucinations, extreme emotions, excited athletic activities and contradictory language, but negative symptoms such as depression, Anorexia, social isolation or memory and attention deficit.

Neurokinin-3 receptor antagonists have been described as useful for pain or inflammation, and schizophrenia (Exp. Opinion. Ther. Patents (2000), 10 (6), 939-969 and Current Opinion in Investigational Drugs, 2001, 2 (7), 950-956 and Psychiatric Disorders Study 4, Schizophrenia, June 2003, Decision Recources, Inc., Waltham, Massachusetts).

It is an object of the present invention to provide a novel compound of formula I, a process for the preparation thereof, a medicament based on the compound according to the invention, a process for the preparation thereof and a pharmaceutical composition for the treatment of depression, pain, bipolar disorder, psychosis, Parkinson's disease, schizophrenia, anxiety or attention deficit hyperactivity To the use of a compound of formula I in the control or prevention of diseases such as behavioral disorders (ADHD).

Preferred indications for use of the compounds of the invention are depression, psychosis, Parkinson's disease, schizophrenia, anxiety and attention deficit hyperactivity disorder (ADHD).

The following definitions of the general terms used herein apply irrespective of whether the terms are used alone or in combination.

The term "lower alkyl" as used herein refers to straight or branched chain alkyl groups containing from 1 to 8 carbon atoms such as methyl, ethyl, propyl, isopropyl, n-butyl, i-butyl, do. Preferred lower alkyl groups are those containing 1 to 4 carbon atoms.

The term "lower alkoxy" as used herein refers to the straight chain or branched chain alkyl group defined above linked to an oxygen atom.

The term "lower alkyl substituted by halogen" shall refer to a substitution in the alkyl group defined above with at least one hydrogen atom is halogen, for example _{-CF 3, -CHF 2, -CH 2} F, -CH 2 CF 3, -C _{(CH 3) 2 CF 3,} -CH (CH 3) CH 2 CF 3, -CH (CH 3) CF 3, -CH 2 CH 2 CF 3, -CH 2 CH 2 CH 2 CF 3, -CH 2 CH ₂ CF ₂ CF ₃ , -CH ₂ CH ₂ CH ₂ CF ₂ CF ₃ , -CH ₂ CF ₂ CF _3, and the like. The lower alkyl group substituted with halogen preferably contains 1 to 5 carbon atoms.

The term "lower alkyl substituted by hydroxy" refers to the replacement of one or more hydrogen atoms in the alkyl groups defined above with hydroxy.

The term "halogen" refers to chlorine, iodine, fluorine and bromine.

The term "cycloalkyl" refers to a saturated carbon ring containing from 3 to 7 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and the like.

The term "aryl" refers to a cyclic aromatic hydrocarbon radical consisting of one or more fused rings containing from 6 to 14 carbon atoms, wherein one or more rings are aromatic, such as phenyl, naphthyl, Tetrahydronaphthalene or indanyl. Preferably a phenyl group.

The term "heteroaryl" means a cyclic aromatic hydrocarbon radical consisting of at least one fused ring containing from 5 to 14 ring atoms, preferably from 5 to 10 ring atoms, wherein at least one ring is aromatic and in the at least one ring, O and S, and includes, for example, quinoxalinyl, dihydroisoquinolinyl, pyrazinyl, pyrazolyl, 2,4-dihydro-pyrazol-3-one, pyridinyl, Isoxazolyl, benzo [1,3] dioxole, [1.3.4] thiadiazole, pyridazinyl, pyrimidinyl, benzotriazol-5-yl, benzoimidazol- , [4] -thiazol-1-yl, [l, 6] naphthyridin-2-yl, imidazo [4,5- b] pyridin- , Tetrazolyl, thiazolyl, thiadiazolyl, thienyl, furyl, imidazo l-1-yl, or benzofuranyl. A preferred heteroaryl group is pyridine-2,3 or 4-yl.

The term "heterocyclic cycloalkyl" refers to a substitution by one or two carbon atoms are N, S or O in the alkylene chain, for example, tetrahydropyranyl, 1,1-dioxo-hexahydro--1λ ^{6-thiopyran-one} , 1,1-dioxo-tetrahydro-1? ⁶ -thiophenyl, Pyrrolidinyl, piperidinyl, tetrahydrofuranyl, tetrahydrothiophenyl, piperidin-4-yl or piperazin-1-yl, 1,1-dioxo-l, ⁶ -thiomorpholinyl.

The term "pharmaceutically acceptable acid addition salts" refers to salts formed with inorganic and organic acids such as hydrochloric acid, nitric acid, sulfuric acid, phosphoric acid, citric acid, formic acid, fumaric acid, maleic acid, acetic acid, succinic acid, And the like.

The following structures are included in Formula I of the present invention:

Claims 1. Compounds of the general formula &lt; RTI ID = 0.0 &gt; (Ia) &lt; / RTI &

(Ia)

In this formula,

R ¹ is hydrogen, halogen, cyano, lower alkyl or lower alkyl substituted by halogen; n is 1, 2 or 3, and when n is 2 or 3, R &lt; ¹ &gt; may be different;

R ² is hydrogen or methyl;

R <^6> is hydrogen, di-lower alkyl or = O;

o and m are independently of each other 0, 1 or 2;

R ^{7 'is} hydrogen, -C (O) - lower alkyl, -C (O) O- lower alkyl, -C (O) CH ₂ O- lower _{alkyl, -C (O) CH 2 CN} , or

-C (O) - cycloalkyl, cycloalkyl, or -CH ₂ - cycloalkyl (wherein the cycloalkyl group is optionally halogen, lower alkoxy, lower alkyl substituted by halogen, cyano, -CH ₂ O- lower alkyl or lower Alkyl), or

-C (O) -heterocycloalkyl or heterocycloalkyl, or

Lower alkoxy, lower alkyl substituted by halogen, C (O) NH-lower alkyl, -C (O) -lower alkyl, _{C (O) NH 2, C} (O) - lower alkyl, S (O) ₂ - lower alkyl or cyano-substituted, and the furnace;

Z is -O-, -NH- or -N (lower alkyl) -;

R ⁴ is lower alkyl, by lower alkyl, cycloalkyl substituted by lower alkyl, hydroxy substituted lower alkyl substituted by halogen, (CH _{2) 2,3} -O- lower _{alkyl, CH (CH 3) CH 2} - O- lower alkyl, (CH _{2) q} CN, bicyclo [2.2.1] heptane-yl, or

Optionally substituted by lower alkyl, lower alkyl, lower alkoxy or halogen-substituted by halogen, (CH _{2) q} - cycloalkyl, or

(CH ₂ ) _q -heterocycloalkyl, (CH ₂ ) _q -aryl, CH (lower alkyl) -aryl, CH (cycloalkyl) -aryl or (CH ₂ ) _q -heteroaryl, , The aryl or heteroaryl ring is optionally substituted with halogen, hydroxy, lower alkyl, lower alkyl substituted by halogen, S (O) ₂ -lower alkyl, cyano or lower alkoxy;

q is 0, 1 or 2;

The compounds of formula (Ia) are as follows:

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- Pyridin-3-yl} -methyl-carbamic acid tert-butyl ester,

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- Pyridin-3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- Pyridin-3-yl} -methyl-carbamic acid cyclopentyl ester,

rac - [(3R, 4S) -1- (1- cyclopropylmethyl-piperidine-4-carbonyl) -4- (3,4-dichloro-phenyl) -pyrrolidin-3-yl] - Methyl-carbamic acid 4-fluoro-phenyl ester,

[(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- 3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [1- (1- methyl- cyclopropanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

rac - [(3R, 4S) -1- (1- cyclopropylmethyl-piperidine-4-carbonyl) -4- (3,4-dichloro-phenyl) -pyrrolidin-3-yl] - Methyl-carbamic acid phenyl ester,

rac - [(3R, 4S) -1- (1- cyclopropylmethyl-piperidine-4-carbonyl) -4- (3,4-dichloro-phenyl) -pyrrolidin-3-yl] - Methyl-carbamic acid p-tolyl ester,

rac - [(3R, 4S) -1- (1- cyclopropylmethyl-piperidine-4-carbonyl) -4- (3,4-dichloro-phenyl) -pyrrolidin-3-yl] - Methyl-carbamic acid 4-methoxy-phenyl ester,

rac - [(3R, 4S) -1- (1- cyclopropylmethyl-piperidine-4-carbonyl) -4- (3,4-dichloro-phenyl) -pyrrolidin-3-yl] - Methyl-carbamic acid 4-chloro-phenyl ester,

rac - [(3R, 4S) -1- (1- cyclopropylmethyl-piperidine-4-carbonyl) -4- (3,4-dichloro-phenyl) -pyrrolidin-3-yl] - Methyl-carbamic acid butyl ester,

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- Pyridin-3-yl} -methyl-carbamic acid 4-chloro-phenyl ester,

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- Pyridin-3-yl} -methyl-carbamic acid phenyl ester,

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- Pyridin-3-yl} -methyl-carbamic acid p-tolyl ester,

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- Pyridin-3-yl} -methyl-carbamic acid p-methoxyphenyl ester,

[(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- 3-yl} -methyl-carbamic acid p-tolyl ester,

(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [1- (1- methyl- cyclopropanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid p-tolyl ester,

[(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- 3-yl} -methyl-carbamic acid 4-chlorophenyl ester,

(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [1- (1- methyl- cyclopropanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid 4-chlorophenyl ester,

Pyrrolidin-3-yl] -methyl-carbamic acid tert-butyl ester [(3R, 4S) Carbamic acid 4-methoxy-phenyl ester,

4-dichloro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid tert- Carbamic acid 4-methoxy-phenyl ester,

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- Pyridin-3-yl} -methyl-carbamic acid 2,2-dimethyl-propyl ester,

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- Pyridin-3-yl} -methyl-carbamic acid prop-2-ynyl ester,

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- Pyridin-3-yl} -methyl-carbamic acid cyclopropylmethyl ester,

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- Pyridin-3-yl} -methyl-carbamic acid 2-cyclopropyl-ethyl ester,

rac - {(3R, 4S) -4- (4-Chloro-phenyl) -l- - yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

rac - {(3R, 4S) -4- (4-Chloro-phenyl) -l- - yl} -methyl-carbamic acid butyl ester,

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- 3-yl} -methyl-carbamic acid 6-chloro-pyridin-3-yl ester,

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- Pyridin-3-yl} -methyl-carbamic acid 3,3,3-trifluoro-propyl ester,

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- Pyridin-3-yl} -methyl-carbamic acid 3,3-dimethyl-butyl ester,

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- Pyridin-3-yl} -methyl-carbamic acid tetrahydro-pyran-4-ylmethyl ester,

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- Pyridin-3-yl} -methyl-carbamic acid cyclopentylmethyl ester,

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- 3-yl} -methyl-carbamic acid 3-methyl-oxetan-3-ylmethyl ester,

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- 3-yl} -methyl-carbamic acid 6-trifluoromethyl-pyridin-3-yl ester,

[(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- 3-yl} -methyl-carbamic acid 2-cyclopropyl-ethyl ester,

(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [1- (1- methyl- cyclopropanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid 2-cyclopropyl-ethyl ester,

Yl) -pyrrolidin-3-yl &lt; / RTI &gt; } -Methyl-carbamic acid 4-fluoro-phenyl ester,

(3S, 4R) -4- (4-chloro-phenyl) -l- [l- (1- methyl- cyclopropanecarbonyl) -piperidine-4- carbonyll- pyrrolidin- } -Methyl-carbamic acid 4-fluoro-phenyl ester,

rac - {(3R, 4R) -4- (3,4-Dichloro-phenyl) Pyridin-3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

[(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- 3-yl} -methyl-carbamic acid 6-chloro-pyridin-3-yl ester,

(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [1- (1- methyl- cyclopropanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid 6-chloro-pyridin-3-yl ester,

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- Pyridin-3-yl} -carbamic acid 4-fluoro-phenyl ester,

rac - {(3R, 4S) -4- (4-Chloro-phenyl) -l- - yl} -methyl-carbamic acid 2-cyclopropyl-ethyl ester,

rac - {(3R, 4S) -4- (4-Chloro-phenyl) -l- -Yl} -methyl-carbamic acid 4-methyl-cyclohexyl ester,

- rac-1 - {(3R, 4S) -4- (4-Chloro-phenyl) Yl} -3- (2-cyclopropyl-ethyl) -l-methyl-urea,

[(3R, 4R) -4- (3,4-Dichloro-phenyl) -l- 3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

(3S, 4S) -4- (3,4-Dichloro-phenyl) -l- 3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

rac - {(3R, 4S) -4- (4-Chloro-phenyl) -l- - yl} -methyl-carbamic acid 2-cyclopropyl-ethyl ester,

rac - {(3R, 4S) -4- (4-Chloro-phenyl) -l- - yl} -methyl-carbamic acid 2-cyclopropyl-ethyl ester,

pyrrolidin-3-yl] -methyl-pyrrolidine-l-carboxylic acid tert-butyl ester as a colorless oil. Carbamic acid 4-fluoro-phenyl ester,

methyl-amino] -pyrrolidine-l- (3S, 4R) -3- (3,4-dichloro-phenyl) -4 - [(4- fluoro-phenoxycarbonyl) Carbonyl} -piperidine-l-carboxylic acid tert-butyl ester,

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- Pyridin-3-yl} -methyl-carbamic acid 4,4,4-trifluoro-butyl ester,

[(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- (3R, 4R) -4- (3,4-Dichloro-phenyl) -pyridin-2-yl] Yl) -methyl-carbamic acid (1R, 2S, 4S) - [Lambda] / - Cyclo [2.2.1] hept-2-yl ester,

[(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- 2R, 4S) -bicyclo [2.2.1] hept-2-yl ester and {(3S, 4R) -4- (3,4- Yl) -methyl-carbamic acid (lR, 2R, 4S) - [Lambda] ^^ - Cyclo [2.2.1] hept-2-yl ester,

rac - {(3R, 4S) -4- (3-Chloro-4-methyl-phenyl) 3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

rac - {(3R, 4S) -4- (4-Chloro-3-methyl-phenyl) 3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

rac - [(3R, 4S) -4- (3,4- dichloro-phenyl) -1- (piperidin-4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4- Fluoro-phenyl ester,

rac - [(3R, 4S) -4- (3,4- dichloro-phenyl) -1- (1-propionyl-piperidine-4-carbonyl) -pyrrolidin-3-yl] -methyl -Carbamic &lt; / RTI &gt; acid 4-fluoro-phenyl ester,

rac - [(3R, 4S) -1- (1- cyclopropane-carbonyl-piperidine-4-carbonyl) -4- (3,4-dichloro-phenyl) -pyrrolidin-3-yl; -Methyl-carbamic acid 4-fluoro-phenyl ester,

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- 3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) - 1- [1- (tetrahydro-pyran-4-carbonyl) -piperidine- 3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- [l- (tetrahydro-pyran-4- yl) -piperidine- Pyridin-3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

rac - [(3R, 4S) -4- (3,4-Dichloro-phenyl) ) -Pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester,

rac - [(3R, 4S) -1- [1- (6- chloro-3-yl) -piperidine-4-carbonyl] -4- (3,4-dichloro-phenyl) - Pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester,

rac - [(3R, 4S) -1- (5'-Cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- Dichloro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester,

[(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- 3-yl} -methyl-carbamic acid 4,4,4-trifluoro-butyl ester,

(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [1- (1- methyl- cyclopropanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid 4,4,4-trifluoro-butyl ester,

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- Pyridin-3-yl} -methyl-carbamic acid 3,3,4,4,4-pentafluoro-butyl ester,

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- (S) -l- (tetrahydro-furan-2-yl) methyl ester and rac - {(3R, 4S) -4- (3,4- 3-yl} -methyl-carbamic acid (R) -1- (Tetra-2-methyl-piperazin-1- Hydro-furan-2-yl) methyl ester,

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- (S) -1- (tetrahydro-furan-3-yl) methyl ester and rac - {(3R, 4S) -4- (3,4- 3-yl} -methyl-carbamic acid (R) -1- (Tetra-2-methyl-piperazin-1- Hydro-furan-3-yl) methyl ester,

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- Pyridin-3-yl} -methyl-carbamic acid 3,3,3-trifluoro-propyl ester,

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- Pyridin-3-yl} -methyl-carbamic acid 3,3,3-trifluoro-propyl ester,

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- Pyridin-3-yl} -methyl-carbamic acid 4,4,5,5,5-pentafluoro-pentyl ester,

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- Pyridin-3-yl} -methyl-carbamic acid 1-methyl-cyclopropylmethyl ester,

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- Pyridin-3-yl} -methyl-carbamic acid 2-methyl-cyclopropylmethyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester,

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- Pyridin-3-yl} -methyl-carbamic acid 4-fluoro-benzyl ester,

rac- 1 - {(3R, 4S) -4- (4-Chloro-phenyl) Yl} -3- (4-fluoro-phenyl) -l-methyl-urea,

rac -l- (2-Cyclopropyl-ethyl) -3 - {(3R, 4S) -4- (3,4- -Piperidine-4-carbonyl] -pyrrolidin-3-yl} -1,3-dimethyl-urea,

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- 3-yl} -methyl-carbamic acid 3-hydroxy-3-methyl-butyl ester,

rac {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- Yl} -methyl-carbamic acid 4,4-difluoro-cyclohexylmethyl ester,

Yl) -pyrrolidin-3-yl &lt; / RTI &gt; } -Methyl-carbamic acid 4,4,4-trifluoro-butyl ester,

(3S, 4R) -4- (4-chloro-phenyl) -l- [l- (1- methyl- cyclopropanecarbonyl) -piperidine-4- carbonyll- pyrrolidin- } -Methyl-carbamic acid 4,4,4-trifluoro-butyl ester,

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- Pyridin-3-yl} -methyl-carbamic acid 4,4-difluoro-cyclohexyl ester,

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- Pyridin-3-yl} -methyl-carbamic acid 4-trifluoromethyl-cyclohexyl ester,

(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [1- (1- methyl- cyclopropanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid l-methyl-cyclopropylmethyl ester,

[(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- 3-yl} -methyl-carbamic acid l-methyl-cyclopropylmethyl ester,

[(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- 3-yl} -methyl-carbamic acid 4-trifluoromethyl-cyclohexyl ester,

(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [1- (1- methyl- cyclopropanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid 4-trifluoromethyl-cyclohexyl ester,

{(3S, 4R) -4- ( 4- chloro-phenyl) -1- [1- (1, 1-dioxo-hexahydro--1λ ^{6-thiopyran-4-yl)} -piperidin-4 Carbonyl] -pyrrolidin-3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

[(3S, 4R) -4- (4-Chloro-phenyl) -l- - yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- Pyridin-3-yl} -methyl-carbamic acid 3,3-difluoro-cyclopentylmethyl ester,

Yl) -piperidine-4-carbonyl] -pyrrolidin-3-yl} - (3S, 4R) } -Methyl-carbamic acid 4-fluoro-phenyl ester,

(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [1- (1- methyl- cyclopropanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid 3-bromo-4-fluoro-phenyl ester,

{(3S, 4R) -4- ( 4- chloro-phenyl) -1- [1- (1,1-dioxo-tetrahydro--1λ ^{6-thiophen-3-yl)} -piperidin-4 Carbonyl] -pyrrolidin-3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

Pyridin-3-yl) -piperidine-4-carbonyl] -pyrrolidin-3 (2S) - yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid tert-butyl ester,

rac - [(3S, 4R) -1- (5'-tert-Butylcarbamoyl-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- (4-chloro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester,

rac - [(3S, 4R) -1- (5'-tert-Butylcarbamoyl-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- (4-chloro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4- trifluoromethyl- cyclohexyl ester,

[(3R, 4S) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester,

[(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [l- (tetrahydro- pyran- 4- yl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid 4-trifluoromethyl-cyclohexyl ester,

rac - [(3S, 4R) -1- (5'-tert-Butylcarbamoyl-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- (4-chloro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4,4,4- trifluoro-butyl ester,

[(3R, 4S) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-trifluoromethyl-cyclohexyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-trifluoromethyl-cyclohexyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4,4,4-trifluoro-butyl ester,

[(3R, 4S) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4,4,4-trifluoro-butyl ester,

[(3S, 4R) -4- (4-fluoro-phenyl) -l- Yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

Piperidin-4-carbonyl] -pyrrolidine-3-carboxylic acid {(3R, 4S) Yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

[(3S, 4R) -1- (5'-Cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- Fluoro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester,

[(3R, 4S) -1- (5'-Cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- Fluoro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester,

Methyl-amino] -pyrrolidine-l-carbonyl} - piperidine-l-carboxylic acid ethyl ester was prepared from 4 - {(3R, 4S) 1-carboxylic acid tert-butyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -l- Yl] -pyrrolidin-3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -l- (piperidine- 4- carboyl) -pyrrolidin-3- yl] -methyl- carbamic acid 4-fluoro-phenyl ester ,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid ethyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid isopropyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid propyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid isobutyl ester,

Pyridin-3-yl) -piperidine-4-carbonyl] -pyrrolidine-l- 3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

(3S, 4R) -4- (4-chloro-phenyl) -l- [l- (1- methyl- cyclopropanecarbonyl) -piperidine-4- carbonyll- pyrrolidin- } -Methyl-carbamic acid isobutyl ester,

(3S, 4R) -4- (4-chloro-phenyl) -l- [l- (1- methyl- cyclopropanecarbonyl) -piperidine-4- carbonyll- pyrrolidin- } -Methyl-carbamic acid propyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid cyclohexyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 3,3,3-trifluoro-propyl ester,

[(3R, 4S) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 3,3,3-trifluoro-propyl ester,

Pyrrolidin-3-yl] -methyl-carbamic acid 4- (4-fluoro-phenyl) Fluoro-phenyl ester,

Methyl-amino] -pyrrolidine-l-carbonyl} -piperidine-l-carboxylic acid tert-butyl ester, L-carboxylic acid tert-butyl ester, &lt; RTI ID = 0.0 &gt;

(3S, 4R) -4- (4-chloro-phenyl) -l- [l- (1- methyl- cyclopropanecarbonyl) -piperidine-4- carbonyll- pyrrolidin- } -Methyl-carbamic acid cyclohexyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid l-cyclopropyl-ethyl ester,

(3S, 4R) -4- (4-chloro-phenyl) -l- [l- (1- methyl- cyclopropanecarbonyl) -piperidine-4- carbonyll- pyrrolidin- } -Methyl-carbamic acid 1-cyclopropyl-ethyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid oxetan-3-yl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid tetrahydro-pyran-4-yl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid tert-butyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 2,2,2-trifluoro-ethyl ester,

[(3S, 4R) -1- (5'-Cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- Dichloro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-trifluoromethyl-cyclohexyl ester,

[(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- Pyridin-3-yl} -methyl-carbamic acid 4-trifluoromethyl-cyclohexyl ester,

(3S, 4R) -4- (4-chloro-phenyl) -l- [l- (1- methyl- cyclopropanecarbonyl) -piperidine-4- carbonyll- pyrrolidin- } -Methyl-carbamic acid tetrahydro-pyran-4-yl ester,

(3S, 4R) -4- (4-chloro-phenyl) -l- [l- (1- methyl- cyclopropanecarbonyl) -piperidine-4- carbonyll- pyrrolidin- } -Methyl-carbamic acid tert-butyl ester,

(3S, 4R) -4- (4-chloro-phenyl) -l- [l- (1- methyl- cyclopropanecarbonyl) -piperidine-4- carbonyll- pyrrolidin- } -Methyl-carbamic acid 2,2,2-trifluoroethyl ester,

(3S, 4R) -4- (4-chloro-phenyl) -l- [l- (1- methyl- cyclopropanecarbonyl) -piperidine-4- carbonyll- pyrrolidin- } -Methyl-carbamic acid 2,2,2-trifluoro-l-methyl-ethyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 2,2,2-trifluoro-l-methyl-ethyl ester,

Yl) -piperidine-4-carbonyl] -pyrrolidin-3 (1 H) -quinolin- - yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -l- (pyrrolidine- 3- carbonyl) -pyrrolidin-3- yl] -methyl- carbamic acid 4- fluoro-phenyl ester ,

Yl) -piperidine-4-carbonyl] -pyrrolidine-1-carboxylic acid tert-butyl ester {(3S, 4R) 3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

Pyrrolidin-3-yl] -methyl-carbamic acid 4- (4-fluoro-phenyl) Fluoro-phenyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -l- (1- cyclopropanecarbonyl- pyrrolidine- 3- carbonyl) -pyrrolidin-3- yl] -methyl- carbamic acid 4-fluoro-phenyl ester,

Pyrrolidine-3-carbonyl] -pyrrolidin-3-yl} - (2-methoxy- Methyl-carbamic acid 4-fluoro-phenyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid cyclobutyl ester,

(3S, 4R) -4- (4-chloro-phenyl) -l- [l- (1- methyl- cyclopropanecarbonyl) -piperidine-4- carbonyll- pyrrolidin- } -Methyl-carbamic acid cyclobutyl ester,

(3S, 4R) -4- (4-chloro-phenyl) -l- [l- (1- methyl- cyclopropanecarbonyl) -piperidine-4- carbonyll- pyrrolidin- } -Methyl-carbamic acid 2,2,3,3-tetrafluorocyclobutyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 2,2,3,3-tetrafluorocyclobutyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 3,3,3-trifluoro-l-methyl-propyl ester,

(3S, 4R) -4- (4-chloro-phenyl) -l- [l- (1- methyl- cyclopropanecarbonyl) -piperidine-4- carbonyll- pyrrolidin- } -Methyl-carbamic acid 3,3,3-trifluoro-l-methyl-propyl ester,

Yl) -pyrrolidine-3-carbonyl] -pyrrolidin-3-yl} - (3- } -Methyl-carbamic acid 4-fluoro-phenyl ester,

[(3S, 4R) -4- (4-Chloro-phenyl) -1- (5'-methanesulfonyl-3,4,5,6-tetrahydro- 4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -l- (5 ' -trifluoromethyl-3,4,5,6-tetrahydro- Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester,

[(3S, 4R) -1- (5'-Acetyl-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester,

Yl] -piperidin-4-carbonyl) -pyrrolidin-3-yl] -methyl- Carbamic acid 4-fluoro-phenyl ester,

Pyrrolidine-4-carbonyl] -pyrrolidin-3-one To a solution of {(3S, 4R) -4- - yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (4'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (3'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester,

Yl) -piperidine-4-carbonyl] -pyrrolidin-3 (2S) - yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -l- (3 ' -chloro-5 ' -trifluoromethyl-3,4,5,6-tetrahydro- -] bipyridinyl-4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4- fluoro-phenyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (6'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester,

[(3S, 4R) -4- (4-Chloro-phenyl) -l- 3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

Yl] -piperidin-4-carbonyl) -pyrrolidin-3-yl] -methyl- Carbamic acid 4-fluoro-phenyl ester,

[(3S, 4R) -4- (4-Chloro-phenyl) -l- 3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

Yl) -piperidine-4-carbonyl] -pyrrolidin-3 (2S) -4- [ - yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -l- (5'-methyl-3,4,5,6-tetrahydro- Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-fluoro-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester,

[(3S, 4R) -1- (5'-Carbamoyl-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- Chloro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester,

Pyridin-3-yl) -piperidine-4-carbonyl] -pyrrolidine-l- 3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (6'-cyano-3,4,5,6-tetrahydro-2H- [1,3 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -l- (5'-chloro-3,4,5,6-tetrahydro- Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid phenyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-methoxy-phenyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid p-tolyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-chloro-phenyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid cyclopentyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 2,2-dimethyl-propyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 2-methoxy-ethyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-trifluoromethyl-phenyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 2,4-difluoro-phenyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 3,4-difluoro-phenyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (6'-cyano-3,4,5,6-tetrahydro-2H- [1,3 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 3,5-difluoro-phenyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 2,3-difluoro-phenyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 2-fluoro-phenyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 2-chloro-phenyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 3-fluoro-propyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid cyclopropylmethyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 3-methoxy-propyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 1-methyl-cyclopropylmethyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 3-methyl-oxetan-3-ylmethyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 2-cyclopropyl-ethyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-methyl-cyclohexyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-methyl-cyclohexyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 2-methoxy-1-methyl-ethyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 2-fluoro-ethyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4- methanesulfonyl-phenyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 3-cyano-phenyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid l- (4-fluoro-phenyl)

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 2-fluoro-l-fluoromethyl-ethyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-cyano-phenyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid o-tolyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid m-tolyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid tetrahydro-pyran-4-ylmethyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid tetrahydro-furan-2-ylmethyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid tetrahydro-furan-3-ylmethyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 1,1-dimethyl-propyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 2,2,2-trifluoro-1,1-dimethyl- ethyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbamoyl) -pyrrolidin-3-yl] -methyl-carbamic acid l- (4-fluoro-phenyl) -propyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-cyano-2-fluoro-phenyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-methoxy-cyclohexyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid cyclopropyl- (4-fluoro-phenyl)

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-methyl-l-trifluoromethyl- cyclohexyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 1,4-dimethyl-cyclohexyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 1,4-dimethyl-cyclohexyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid l-methyl-cyclopentyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 5-chloro-pyridin-2-

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-cyano-3-fluoro-phenyl ester,

4-carbonyl) -4- (4-chloro-phenyl) -pyrrolidin-3- yl] -methyl-carbamic acid 4- fluoro Phenyl-ester,

4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid &lt; / RTI &gt; 4-fluoro-phenyl ester,

[(3S, 4R) -4- (4-Chloro-phenyl) -l- 3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -l- [l- (3- fluoro-cyclobutanecarbonyl) -piperidine- 4- carbonyl] -pyrrolidin- Yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -l- [l- (3,3- difluoro-cyclobutanecarbonyl) -piperidine-4- carbonyl] -pyrrolidine Yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

(3S, 4R) -4- (4-chloro-phenyl) -l- [l- (3- methoxy- cyclobutanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- Yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

[(3S, 4R) -4- (4-Chloro-phenyl) -l- [1- (1- trifluoromethyl- cyclobutanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

4-carbonyl] -pyrrolidin-3-yl} - (2-cyano-acetyl) -piperidine- Methyl-carbamic acid 4-fluoro-phenyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -l- [1- (1- cyano- cyclopropanecarbonyl) -piperidine- 4- carbonyl] -pyrrolidin- Yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

[(3S, 4R) -4- (4-Chloro-phenyl) -l- l- (l- trifluoromethyl- cyclopropanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

{(3S, 4R) -4- (4-Chloro-phenyl) -l- [l- (2,2- difluoro- cyclopropanecarbonyl) -piperidine- 4- carbonyl] -pyrrolidine Yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -l- [l- (tetrahydro-pyran-4-carbonyl) -piperidine- 4- carbonyl] -pyrrolidin- Yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

4- (4-chloro-phenyl) -l- [l- (2,2-dimethyl-tetrahydro-pyran-4-carbonyl) -piperidine- -Pyrrolidin-3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -l- [l- (1- methoxymethyl- cyclopropanecarbonyl) -piperidine-4- carbonyl] -pyrrolidin- - yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -l- [l- (2,2- dimethyl- cyclopropanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

[(3S, 4R) -4- (4-Chloro-phenyl) -l- [1- (5- trifluoromethyl- pyridine- 2- carbonyl) -piperidine-4- carbonyl] -pyrrole Pyridin-3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

Pyridin-2-carbonyl) -piperidine-4-carbonyl] -pyrrolidine-l- 3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

{(3S, 4R) -4- (4-Chloro-phenyl) -l- Yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

[(3S, 4R) -4- (4-Chloro-phenyl) -l- [1- (1-isopropyl-6-oxo-piperidine- 3- carbonyl) -piperidine- ] -Pyrrolidin-3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

- [(3S, 4R) -1- (1-cyclobutanecarbonyl-piperidine-4- carbonyl) -4- (3,4- dichloro- phenyl) -pyrrolidin- -Carbamic &lt; / RTI &gt; acid 4-fluoro-phenyl ester,

[(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- 3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [l- (3-fluoro- cyclobutanecarbonyl) -piperidine-4- carbonyl] -pyrrolidine Yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

- (3,3-difluoro-cyclobutanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidin-3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [l- (3- methoxy- cyclobutanecarbonyl) -piperidine-4- carbonyl] -pyrrolidine Yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

[(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- 3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

[(3S, 4R) -1- [1- (2-cyano-acetyl) -piperidine-4- carbonyl] -4- (3,4- dichloro- phenyl) -pyrrolidin- Yl-methyl-carbamic acid 4-fluoro-phenyl ester,

[(3S, 4R) -1- [1- (1 -cyano-cyclopropanecarbonyl) -piperidine-4- carbonyl] -4- (3,4- dichloro- phenyl) -pyrrolidine Yl] -methyl-carbamic acid 4-fluoro-phenyl ester,

[(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- 3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

[(3S, 4R) -4- (3,4-Dichloro-phenyl) -1- [1- (2,2- difluoro- cyclopropanecarbonyl) -piperidine- Pyrrolidin-3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [l- (tetrahydro-pyran- Yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

4- (3,4-Dichloro-phenyl) -l- [l- (2,2-dimethyl-tetrahydro-pyran-4-carbonyl) -piperidin- Carbonyl] -pyrrolidin-3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [l- (1- methoxymethyl- cyclopropanecarbonyl) -piperidine-4- carbonyl] -pyrrole Pyridin-3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

[(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [l- (2,2- dimethyl- cyclopropanecarbonyl) -piperidine- 3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

[(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- -Pyrrolidin-3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

[(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- 3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

[(3S, 4R) -4- (3,4-Dichloro-phenyl) -1- [1- (6-oxo-piperidine- Pyrrolidin-3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

- (l-isopropyl-6-oxo-piperidine-3-carbonyl) -piperidin-4 - carbonyl] -pyrrolidin-3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

4- [(3,4-dichloro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester,

4-carbonyl] -4- (4-fluoro-phenyl) -pyrrolidin-3-yl] -Methyl-carbamic acid 4-fluoro-phenyl ester,

4-carbonyl) -4- (4-fluoro-phenyl) -pyrrolidin-3- yl] -methyl- carbamic acid 4- Fluoro-phenyl ester,

[(3S, 4R) -4- (4-fluoro-phenyl) -l- Yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

4- [4- (4-fluoro-phenyl) -pyrrolidin-3-yl] -Yl] -methyl-carbamic acid 4-fluoro-phenyl ester,

4- [4- (4-fluoro-phenyl) -pyrrolidin-3-yl] -Yl] -methyl-carbamic acid 4-fluoro-phenyl ester,

[(3S, 4R) -4- (4-fluoro-phenyl) -l- [1- (1- trifluoromethyl- cyclobutanecarbonyl) -piperidine-4- carbonyl] -pyrrolidine Yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

[(3S, 4R) -4- (4-fluoro-phenyl) -l- 3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

{(3S, 4R) -4- (4-fluoro-phenyl) -1- [1- (6-oxo- piperidine-3- carbonyl) -piperidine-4- carbonyl] Pyridin-3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

[(3S, 4R) -4- (3,4-Dichloro-phenyl) -1- [1 - ((S) -4-oxo-azetidine- Yl] -pyrrolidin-3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [1- (1- methyl- cyclopropanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid 2-fluoro-pyridin-3-yl ester,

(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [1- (1- methyl- cyclopropanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid 2,6-dimethyl-pyridin-4-yl ester,

(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [1- (1- methyl- cyclopropanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid pyridin-3-yl ester,

(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [1- (1- methyl- cyclopropanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid 6-methyl-pyridin-3-yl ester,

(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [1- (1- methyl- cyclopropanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid pyridin-4-yl ester,

(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [1- (1- methyl- cyclopropanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid 2,6-dimethyl-pyridin-3-yl ester,

(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [1- (1- methyl- cyclopropanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid 5-fluoro-pyridin-3-yl ester,

(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [1- (1- methyl- cyclopropanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid 6-chloro-pyridin-2-yl ester,

(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [1- (1- methyl- cyclopropanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid 2-chloro-5-fluoro-pyridin-3-

(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [1- (1- methyl- cyclopropanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid 2-chloro-pyridin-3-yl ester,

(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [1- (1- methyl- cyclopropanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid 6-trifluoromethyl-pyridin-3-yl ester,

(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [1- (1- methyl- cyclopropanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid 2-cyano-pyridin-3-yl ester,

(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [1- (1- methyl- cyclopropanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid 2-fluoro-6-methyl-pyridin-3-

[(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- (5 ' -trifluoromethyl-3,4,5,6-tetrahydro- 4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester,

[(3S, 4R) -1- (5'-Acetyl-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl-4-carbonyl) -4- -Dichloro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester,

[(3S, 4R) -1- (5'-Chloro-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl-4-carbonyl) -4- -Dichloro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester,

[(3S, 4R) -4- (3,4-Dichloro-phenyl) -1- (5'-fluoro-3,4,5,6-tetrahydro-2H- [ Yl-4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester,

[(3S, 4R) -1- (5'-Carbamoyl-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- Dichloro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester,

Fluoro-3,4,5,6-tetrahydro-2H- [1,2 '] - 4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester,

[(3S, 4R) -4- (4-chloro-3-fluoro-phenyl) Pyridin-4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4- fluoro-phenyl ester,

[(3S, 4R) -4- (4-chloro-3-fluoro-phenyl) -l- (5 ' -trifluoromethyl-3,4,5,6-tetrahydro- -] bipyridinyl-4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4- fluoro-phenyl ester,

[(3S, 4R) -1- (5'-Acetyl-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -3-fluoro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4- fluoro-phenyl ester,

[(3S, 4R) -4- (3-Chloro-4-fluoro-phenyl) 4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester,

[(3S, 4R) -4- (3-Chloro-4-fluoro-phenyl) -l- (5'-chloro-3,4,5,6-tetrahydro- Pyridin-4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4- fluoro-phenyl ester,

[(3S, 4R) -4- (3-Chloro-4-fluoro-phenyl) -l- (5 ' -trifluoromethyl-3,4,5,6-tetrahydro- -] bipyridinyl-4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4- fluoro-phenyl ester,

[(3S, 4R) -1- (5'-Acetyl-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -4-fluoro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4- fluoro-phenyl ester,

- (S) -4-oxo-azetidine-2-carbonyl) -piperidine-4-carbonyl] - Pyrrolidin-3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-hydroxy-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester, or

Methyl-amino] -pyrrolidine-1-carbonyl} - (4-chloro-phenyl) -4 - [(4- fluoro-phenoxycarbonyl) 3,4,5,6-Tetrahydro-2H- [1,2 '] bipyridinyl-5'-yl ester.

Claims 1. A compound of formula (Ib): &lt; EMI ID =

(Ib)

In this formula,

R ¹ is hydrogen, halogen, cyano, lower alkyl or lower alkyl substituted by halogen; n is 1, 2 or 3, and when n is 2 or 3, R &lt; ¹ &gt; may be different;

R ² is hydrogen or methyl;

R <^6> is hydrogen, di-lower alkyl or = O;

o and m are independently of each other 0, 1 or 2;

R is hydrogen, halogen, or lower alkyl;

R ⁷ is hydrogen, halogen, hydroxy, lower alkyl substituted by hydroxy, cyano, or lower alkoxy;

R ⁴ is lower alkyl, by lower alkyl, cycloalkyl substituted by lower alkyl, hydroxy substituted lower alkyl substituted by halogen, (CH _{2) 2,3} -O- lower _{alkyl, CH (CH 3) CH 2} - O- lower alkyl, (CH _{2) q} CN, bicyclo [2.2.1] heptane-yl, or

Optionally substituted by lower alkyl, lower alkyl, lower alkoxy or halogen-substituted by halogen, (CH _{2) q} - cycloalkyl, or

(CH ₂ ) _q -heterocycloalkyl, (CH ₂ ) _q -aryl, CH (lower alkyl) -aryl, CH (cycloalkyl) -aryl or (CH ₂ ) _q -heteroaryl, , The aryl or heteroaryl ring is optionally substituted with halogen, hydroxy, lower alkyl, lower alkyl substituted by halogen, S (O) ₂ -lower alkyl, cyano or lower alkoxy;

q is 0, 1 or 2;

Compounds of formula (Ib) are as follows:

[(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- (trans-4-hydroxy- cyclohexanecarbonyl) -pyrrolidin-3- yl] -methyl- carbamic acid 4 - fluoro-phenyl ester,

[(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- (trans-4-hydroxy-cyclohexanecarbonyl) -pyrrolidin- - fluoro-phenyl ester,

(cis-4-hydroxy-cyclohexanecarbonyl) -pyrrolidin-3-yl] -methyl-carbaldehyde 4-fluoro-phenyl ester,

yl) -methyl-carbaldehyde &lt; RTI ID = 0.0 &gt; (3-methoxy-phenyl) 4-fluoro-phenyl ester,

(trans-4-hydroxy-4-methyl-cyclohexanecarbonyl) -pyrrolidin-3-yl] -Methyl-carbamic acid 4-fluoro-phenyl ester,

(cis-4-hydroxy-4-methyl-cyclohexanecarbonyl) -pyrrolidin-3-yl] -Methyl-carbamic acid 4-fluoro-phenyl ester,

- [(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- (cis-4-hydroxy- cyclohexanecarbonyl) -pyrrolidin- - fluoro-phenyl ester,

 [(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- (cis-4-hydroxy- cyclohexanecarbonyl) -pyrrolidin- - fluoro-phenyl ester,

Pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl} -piperidine-l- Esther,

[(3S, 4R) -4- (4-chloro-phenyl) -l- (4-cyano- cyclohexanecarbonyl) -pyrrolidin-3- yl] -methyl- carbamic acid 4- Esther,

[(3S, 4R) -4- (4-chloro-phenyl) -l- (4- hydroxymethyl- cyclohexanecarbonyl) -pyrrolidin-3- yl] -methyl- carbamic acid 4- Phenyl ester,

[(3S, 4R) -4- (4-chloro-phenyl) -l- (4,4- difluoro- cyclohexanecarbonyl) -pyrrolidin- 3-yl] -methyl- carbamic acid 4- Phenyl-ester,

Pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl} -piperidine-l- Esther.

Claims 1. A compound of formula (Ic) or a pharmaceutically acceptable salt thereof:

(Ic)

In this formula,

R ¹ is hydrogen, halogen, cyano, lower alkyl or lower alkyl substituted by halogen; n is 1, 2 or 3, and when n is 2 or 3, R &lt; ¹ &gt; may be different;

R ² is hydrogen or methyl;

p is 0, 1 or 2;

R ⁴ is lower alkyl, by lower alkyl, cycloalkyl substituted by lower alkyl, hydroxy substituted lower alkyl substituted by halogen, (CH _{2) 2,3} -O- lower _{alkyl, CH (CH 3) CH 2} - O- lower alkyl, (CH _{2) q} CN, bicyclo [2.2.1] heptane-yl,

Optionally substituted by lower alkyl, lower alkyl, lower alkoxy or halogen-substituted by halogen, (CH _{2) q} - cycloalkyl, or

(CH ₂ ) _q -heterocycloalkyl, (CH ₂ ) _q -aryl, CH (lower alkyl) -aryl, CH (cycloalkyl) -aryl or (CH ₂ ) _q -heteroaryl, , The aryl or heteroaryl ring is optionally substituted with halogen, hydroxy, lower alkyl, lower alkyl substituted by halogen, S (O) ₂ -lower alkyl, cyano or lower alkoxy;

q is 0, 1 or 2;

Compounds of formula (Ic) are as follows:

(morpholine-4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro Phenyl-ester,

- [(3S, 4R) -4- (4-chloro-phenyl) -l- (3- morpholin- 4- yl- propionyl) -pyrrolidin- 3- yl] -methyl- carbamic acid 4- fluoro - phenyl ester.

Claims 1. A compound of formula &lt; RTI ID = 0.0 &gt; (Id) &lt; / RTI &

(Id)

In this formula,

R ¹ is hydrogen, halogen, cyano, lower alkyl or lower alkyl substituted by halogen; n is 1, 2 or 3, and when n is 2 or 3, R &lt; ¹ &gt; may be different;

R ² is hydrogen or methyl;

R <^6> is hydrogen, di-lower alkyl or = O;

o and m are independently of each other 0, 1 or 2;

R ⁴ is lower alkyl, by lower alkyl, cycloalkyl substituted by lower alkyl, hydroxy substituted lower alkyl substituted by halogen, (CH _{2) 2,3} -O- lower _{alkyl, CH (CH 3) CH 2} - O- lower alkyl, (CH _{2) q} CN, bicyclo [2.2.1] heptane-yl, or

Optionally substituted by lower alkyl, lower alkyl, lower alkoxy or halogen-substituted by halogen, (CH _{2) q} - cycloalkyl, or

(CH ₂ ) _q -heterocycloalkyl, (CH ₂ ) _q -aryl, CH (lower alkyl) -aryl, CH (cycloalkyl) -aryl or (CH ₂ ) _q -heteroaryl, , The aryl or heteroaryl ring is optionally substituted with halogen, hydroxy, lower alkyl, lower alkyl substituted by halogen, S (O) ₂ -lower alkyl, cyano or lower alkoxy;

q is 0, 1 or 2;

The compounds of formula (Id) are as follows:

4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4 &lt; RTI ID = 0.0 &gt; - fluoro-phenyl ester,

Pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-4-fluoro-4- Phenyl-ester,

[(3S, 4R) -4- (3,4-Dichloro-phenyl) - l- (tetrahydro-pyran- Phenyl-ester,

Pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl (2-methyl- Esther,

4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid tert-butyl ester was prepared in analogy to the procedure described for the synthesis of [(3S, 4R) -4- 4-fluoro-phenyl ester,

Pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl) -phenyl] - Esther,

Pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl} -pyrrolidine The title compound was prepared in analogy to the procedure described for the synthesis of [(3S, 4R) -4- Esther,

Pyrrolidin-3-yl] -methyl-carbamic acid 4-tricyclo [6.3.1.0 &lt; 2 &gt; Fluoromethyl-cyclohexyl ester.

Claims 1. Compounds of the general formula &lt; RTI ID = 0.0 &gt; (Ie) &lt; / RTI &

(Ie)

In this formula,

R ¹ is hydrogen, halogen, cyano, lower alkyl or lower alkyl substituted by halogen; n is 1, 2 or 3, and when n is 2 or 3, R &lt; ¹ &gt; may be different;

R ² is hydrogen or methyl;

R ⁴ is lower alkyl, by lower alkyl, cycloalkyl substituted by lower alkyl, hydroxy substituted lower alkyl substituted by halogen, (CH _{2) 2,3} -O- lower _{alkyl, CH (CH 3) CH 2} - O- lower alkyl, (CH _{2) q} CN, bicyclo [2.2.1] heptane-yl, or

Optionally substituted by lower alkyl, lower alkyl, lower alkoxy or halogen-substituted by halogen, (CH _{2) q} - cycloalkyl, or

(CH ₂ ) _q -heterocycloalkyl, (CH ₂ ) _q -aryl, CH (lower alkyl) -aryl, CH (cycloalkyl) -aryl or (CH ₂ ) _q -heteroaryl, , The aryl or heteroaryl ring is optionally substituted with halogen, hydroxy, lower alkyl, lower alkyl substituted by halogen, S (O) ₂ -lower alkyl, cyano or lower alkoxy;

q is 0, 1 or 2;

The compounds of formula (Ie) are as follows:

pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-4-fluoro-4- Phenyl ester.

Claims 1. A compound of formula (If) or a pharmaceutically acceptable salt thereof:

(If)

In this formula,

R ¹ is hydrogen, halogen, cyano, lower alkyl or lower alkyl substituted by halogen; n is 1, 2 or 3, and when n is 2 or 3, R &lt; ¹ &gt; may be different;

R ² is hydrogen or methyl;

R <^6> is hydrogen, di-lower alkyl or = O;

o and m are independently of each other 0, 1 or 2;

R ⁴ is lower alkyl, by lower alkyl, cycloalkyl substituted by lower alkyl, hydroxy substituted lower alkyl substituted by halogen, (CH _{2) 2,3} -O- lower _{alkyl, CH (CH 3) CH 2} - O- lower alkyl, (CH _{2) q} CN, bicyclo [2.2.1] heptane-yl, or

Optionally substituted by lower alkyl, lower alkyl, lower alkoxy or halogen-substituted by halogen, (CH _{2) q} - cycloalkyl, or

(CH ₂ ) _q -heterocycloalkyl, (CH ₂ ) _q -aryl, CH (lower alkyl) -aryl, CH (cycloalkyl) -aryl or (CH ₂ ) _q -heteroaryl, , The aryl or heteroaryl ring is optionally substituted with halogen, hydroxy, lower alkyl, lower alkyl substituted by halogen, S (O) ₂ -lower alkyl, cyano or lower alkoxy;

q is 0, 1 or 2;

The compounds of formula If are as follows:

- [(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- (cis-4-hydroxy- cyclohexanecarbonyl) -pyrrolidin- -Fluoro-phenyl &lt; / RTI &gt; ester.

Claims 1. A compound of formula (Ig): &lt; EMI ID =

[Chemical Formula Ig]

In this formula,

R ¹ is hydrogen, halogen, cyano, lower alkyl or lower alkyl substituted by halogen; n is 1, 2 or 3, and when n is 2 or 3, R &lt; ¹ &gt; may be different;

R ² is hydrogen or methyl;

R <^6> is hydrogen, di-lower alkyl or = O;

o and m are independently of each other 0, 1 or 2;

R ⁴ is lower alkyl, by lower alkyl, cycloalkyl substituted by lower alkyl, hydroxy substituted lower alkyl substituted by halogen, (CH _{2) 2,3} -O- lower _{alkyl, CH (CH 3) CH 2} - O- lower alkyl, (CH _{2) q} CN, bicyclo [2.2.1] heptane-yl, or

Optionally substituted by lower alkyl, lower alkyl, lower alkoxy or halogen-substituted by halogen, (CH _{2) q} - cycloalkyl, or

(CH ₂ ) _q -heterocycloalkyl, (CH ₂ ) _q -aryl, CH (lower alkyl) -aryl, CH (cycloalkyl) -aryl or (CH ₂ ) _q -heteroaryl, , The aryl or heteroaryl ring is optionally substituted with halogen, hydroxy, lower alkyl, lower alkyl substituted by halogen, S (O) ₂ -lower alkyl, cyano or lower alkoxy;

q is 0, 1 or 2;

The compounds of formula (Ig) are as follows:

[(3S, 4R) -4- ( 4- chloro-phenyl) -1- (1,1-dioxo-hexahydro--1λ ^{6-thiopyran-4-carbonyl)} -pyrrolidin-3-yl; -Methyl-carbamic acid 4-fluoro-phenyl ester.

Another embodiment of the present invention is a compound of formula II: &lt; EMI ID =

&Lt; RTI ID = 0.0 &

In this formula,

R ¹ is hydrogen, halogen, cyano, lower alkyl or lower alkyl substituted by halogen; n is 1, 2 or 3, and when n is 2 or 3, R &lt; ¹ &gt; may be different;

R ² is hydrogen or methyl;

이고, 여기서R ³ is (CH ₂ ) _r C (O) NH ₂ , wherein r is 1 or 2, or a non-aromatic heterocyclic group

, Where

X is N or CH;

Y is ^{-C (R) (R 7)} -, -N (R 7 ') -, -S (O) 2 or O;

R <^6> is hydrogen, di-lower alkyl or = O;

o and m are independently of each other 0, 1 or 2;

p is 0, 1 or 2;

R is hydrogen, halogen, or lower alkyl;

R ⁷ is hydrogen, halogen, hydroxy, lower alkyl substituted by hydroxy, cyano, or lower alkoxy;

R ⁷ is selected from the group consisting of hydrogen, -C (O) -lower alkyl, -C (O) O-lower alkyl, -C (O) CH ₂ O -lower alkyl or cycloalkyl, -CH ₂ -cycloalkyl or -C (O) -cycloalkyl, wherein said cycloalkyl group is optionally substituted by lower alkyl, or -C (O) -heterocycloalkyl, heterocycloalkyl, or heteroaryl, wherein said heterocycloalkyl or heteroaryl group is optionally substituted with optionally halogen, lower alkyl, lower alkoxy, lower alkyl substituted by halogen, C (O) NH- lower _{alkyl, C (O) NH 2,} C (O) - lower alkyl, S (O) ₂ - lower alkyl, or cyano, Lt; / RTI &gt;

Z is -O-, -NH- or -N (lower alkyl) -;

R ⁴ is lower alkyl, by lower alkyl, cycloalkyl substituted by lower alkyl, hydroxy substituted lower alkyl substituted by halogen, (CH _{2) 2,3} -O- lower _{alkyl, CH (CH 3) CH 2} - O- lower alkyl, (CH _{2) q} CN, bicyclo [2.2.1] heptane-yl, or

Optionally substituted by lower alkyl, lower alkyl, lower alkoxy or halogen-substituted by halogen, (CH _{2) q} - cycloalkyl, or

(CH ₂ ) _q -heterocycloalkyl, (CH ₂ ) _q -aryl, CH (lower alkyl) -aryl, CH (cycloalkyl) -aryl or (CH ₂ ) _q -heteroaryl, , The aryl or heteroaryl ring is optionally substituted with halogen, hydroxy, lower alkyl, lower alkyl substituted by halogen, S (O) ₂ -lower alkyl, cyano or lower alkoxy;

q is 0, 1 or 2;

Preferred compounds of formula I are those, wherein R &lt; ² &gt; is methyl.

The compounds of formula (I) and pharmaceutically acceptable salts thereof of the present invention may be prepared by the following method,

comprising the steps of: a) coupling a compound of formula (II) with a suitable carbamoyl chloride, acid chloride or carboxylic acid to obtain a compound of formula

If necessary, converting the compound obtained into a pharmaceutically acceptable acid addition salt; or

b) coupling a compound of formula (II) with a corresponding chloroformate, acid anhydride, or triphosgene and a corresponding alcohol or mixture of amines to obtain a compound of formula

If necessary, converting the compound obtained into a pharmaceutically acceptable acid addition salt

Lt; / RTI &gt;

(I)

&Lt; RTI ID = 0.0 &

(III)

In this formula,

The substituents R ¹ , R ² , R ³ , R ⁴ and Z, and n are as defined above.

The following schemes 1 and 2 describe in more detail the preparation of compounds of formula I. The starting materials of formula (II) are known compounds and can be prepared according to methods known in the art.

Scheme 1

Wherein the substituents R ¹ , R ² , R ³ , R ⁴ and Z are as defined above.

According to Scheme 1, a mixture of the 2-nitrostyrene derivative IV and N- (methoxymethyl) -N- (phenylmethyl) -N- (trimethylsilyl) methylamine V in the presence of a catalytic amount of an acid such as TFA, 3,4-disubstituted pyrrolidine VI is prepared via a stereospecific 1,3-dipolar cycloaddition reaction between the azomethine ylide produced in the presence of a catalyst. Reduction of the nitro moiety of VI using standard conditions such as SnCl ₂ .H ₂ O provides VII . The amino moiety of VII is then alkylated to produce VIII . Reduction of VIII with acid anhydride, chloroformate or triphosgene and a mixture of alcohols or amines in the presence of a base gives IX . The selective N-debenzylation reaction is then carried out using some known procedures that are compatible with the substitution patterns of the aromatic rings to give II . Finally, the derivative I is coupled with the appropriate carbamoyl chloride, acid chloride or carboxylic acid. Alternatively, coupling of the pyrrolidine II with the corresponding acid gives the compound of formula IA , which is deprotected to give the piperidine of formula IB , which is further derivatized to give the final compound of formula I .

Reaction formula  2

Wherein the substituents R ¹ , R ² , R ³ , R ⁴ and Z are as defined above.

According to Scheme 2, the secondary amine of intermediate VII is deprotected, for example, with a Boc group to give the compound of formula X followed by selective debenzylation to yield XI . Subsequently, coupling with suitable carbamoyl chloride, acid chloride or carboxylic acid provides XII . TFA to give the free amine XIII , which is reacted with an acid anhydride, a chloroformate or a triphosgene in the presence of a base and a mixture of an alcohol or an amine to give a derivative of formula ( I ).

Example  One

rac - {(3R, 4S) -4- (3,4-dichloro-phenyl) -l- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  Tert-butyl ester

a) rac - (3R, 4S) -l-Benzyl-3- (3,4-dichloro-phenyl) Pyrrolidine

A solution of N- (methoxymethyl) -N- (phenylmethyl) -N- (trimethylsilyl) methylamine (32.50 g, 0.135 mol) in CH ₂ Cl ₂ (70 mL) _{CH 2 Cl 2 (160 mL)} 1,2- dichloro of -4 - ((E) -2- nitro-vinyl) -benzene (19.60 g, 0.09 mol) and acetic acid (1.54 mL, 0.013 mol) trifluoro Lt; / RTI &gt; The ice bath was removed and the solution was stirred at 25 &lt; 0 &gt; C for an additional 48 h. It was then concentrated and purified by flash chromatography (SiO ₂ , EtOAc / H 1: 6) to afford 25.0 g (79%) of the title compound as yellow oil. ES-MS m / e: 351.0 (M + H ^& lt ^{; +} & gt ^; ).

b) rac - (3S, 4R) -l-Benzyl-4- (3,4-dichloro-phenyl) - Pyrrolidine -3- Yl amine

To a stirred solution of rac- (3R, 4S) -l-benzyl-3- (3,4-dichloro-phenyl) -4-nitro-pyrrolidine (11.60 g, 33.0 mmol) in EtOAc (200 mL) the _{SnCl 2 .2H 2 O (37.26 g} , 0.165 mol) was added to the fraction. The reaction mixture was then heated to reflux for 4 h, cooled to ambient temperature, was added a saturated aqueous solution of NaHCO _3. The salt was filtered off and the product was extracted with EtOAc. Then, the organic phase was dried over Na ₂ SO _4, rac of concentrated in vacuo to afford 5.7 g (54%) - ( 3S, 4R) -1- benzyl-4- (3,4-dichloro-phenyl) -pyrrolidin 3-ylamine &lt; / RTI &gt; as a yellow oil. The product was then used in the next step without further purification. ES-MS m / e: 321.2 (M + H ^& lt ^{; +} & gt ^; ).

c) rac - [(3S, 4R) -l-benzyl-4- (3,4-dichloro-phenyl) - Pyrrolidine -3 days]- methyl - amine

To a solution of rac- (3S, 4R) -l-benzyl-4- (3,4-dichloro-phenyl) -pyrrolidin-3-ylamine (0.54 g, 1.68 mmol) in THF (5 mL) _A solution of K ₂ CO _{3 (} 0.46 g, 3.36 mmol) in ₂ O (3 mL) was added. After 10 minutes, ethyl chloroformate (0.18 mL, 1.85 mmol) was added and stirring was continued at ambient temperature for a further 2 hours. The intermediate carbamate was then extracted with Et ₂ O, dried over Na ₂ SO ₄ and concentrated in vacuo to give a viscous oil. The oil was aspirated into THF (5 mL) and a solution of borane (6.7 mL) in THF (1 M) was added. The reaction mixture was then heated to 65 [deg.] C overnight, cooled to ambient temperature, concentrated and carefully quenched with HCl (5 mL). Then, the mixture was heated to 80 ℃ for 2 hours, cooled to ambient temperature and concentrated in vacuo, diluted with Et ₂ O (20 mL), and neutralized with NaHCO ₃ aqueous solution. The organic phase was dried over Na ₂ SO ₄ and the product was purified by flash chromatography (SiO ₂ , CH ₂ Cl ₂ / MeOH 9: 1) to give 0.29 g (51%) of rac - [(3S, 4R) Benzyl-4- (3,4-dichloro-phenyl) -pyrrolidin-3-yl] -methyl- amine as colorless oil. ES-MS m / e: 335.3 (M + H ^& lt ^{; +} & gt ^; ).

d) rac - [(3R, 4S) -1- benzyl-4- (3,4-dichloro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid tert-butyl ester

To a solution of rac - [(3S, 4R) -l-benzyl-4- (3,4-dichloro-phenyl) -pyrrolidin-3- yl] -methyl- amine ( 2.85 g, 8.50 mmol) was added triethylamine (2.4 mL, 17.0 mmol), 4-dimethylaminopyridine (0.10 g, 0.85 mmol) and di-tert- butyl-dicarbonate (2.04 g, 9.35 mmol ). The solution was stirred at ambient temperature for 2 hours. The solution was diluted with water (30 mL). The organic layer was washed with water (30 mL) and the aqueous layer was extracted with dichloromethane (20 mL), dried over sodium sulfate and concentrated. Purification by chromatography (SiO _2, heptane: ethyl acetate = 100: 0 to 60: 40) to give the title compound (3.52 g, 95%) as a light brown oil. MS m / e: 435.2 [M + H] &lt; ⁺ &gt;.

e) rac - [(3R, 4S) -4- (3,4-dichloro-phenyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  Tert-butyl ester

To a solution of rac - [(3R, 4S) -l-benzyl-4- (3,4-dichloro-phenyl) -pyrrolidin-3- yl] -methyl- carbamic acid tert- -Butyl ester (3.50 g, 8.04 mmol) in THF (20 mL) was added N, N-diisopropylethylamine (1.86 mL, 10.9 mmol). The flask was cooled in a water bath and 1-chloroethyl chloroformate (1.14 mL, 10.5 mmol) was added over 2 min. After stirring at ambient temperature for 2 hours, the solution was allowed to stand at 5 [deg.] C overnight. The reaction mixture was concentrated in vacuo. Methanol (50 mL) was added, which was then stirred at ambient temperature for 4 hours. Concentration gave the title compound (2.95 g, 99%) as a light brown oil. MS m / e: 345.1 [M + H] &lt; ⁺ &gt;.

f) rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) Cyclopropane Yl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  Tert-butyl ester

To a solution of rac - [(3R, 4S) -4- (3,4-dichloro-phenyl) -pyrrolidin-3- yl] -methyl-carbamic acid tert- butyl ester ( N-diisopropylethylamine (8.26 mL, 48.2 mmol), 1- (1-methyl-cyclopropanecarbonyl) -piperidine-4-carboxylic acid (2.78 g, 8.04 mmol) and O- (7-azabenzotriazol-l-yl) -N, N, N ', N'-tetramethyluronium hexafluorophosphate (3.67 g, 9.65 mmol). The resulting solution was stirred at ambient temperature for 6 hours. After diluting with EtOAc (50 mL), the solution was washed twice with water (50 mL) and brine (50 mL). The aqueous layer was extracted with EtOAc (50 mL) and dried over sodium sulfate. Concentrated and chromatographed to give the (SiO _2, heptane: ethyl acetate: methanol = 80:: 20 0 to 0:90:10) to yield the title compound (3.06 g, 75%) was obtained as a light brown foam (foam). MS m / e: 538.3 [M + H] &lt; ⁺ &gt;.

Example  2

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) Cyclopropane carbon Yl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

a) rac - {4 - [(3S, 4R) -3- (3,4-dichloro-phenyl) -4- Methyl amino - Pyrrolidine Carbonyl] -piperidin-1-yl} - (1- methyl - Cyclopropyl )-methane

To a solution of rac - {(3R, 4S) -4- (3,4-dichloro-phenyl) -l- [1- (1-methyl-cyclopropanecarbonyl) Yl) -methyl-carbamic acid tert-butyl ester (3.02 g, 5.61 mmol) in dichloromethane (5 mL) was added triflu or o acetic acid (4.3 mL, 56 mmol ) Was added and stirred at this temperature for 20 hours. The reaction mixture was slowly added to an aqueous solution of sodium carbonate (1M, 60 mL). The organic layer was separated and washed with brine (50 mL). The aqueous layer was extracted with dichloromethane (30 mL), dried over sodium sulfate and concentrated. Purification by chromatography (SiO _2, heptane: ethyl acetate: methanol = 50:: 50 0 to 0:90:10) to afford the title compound (1.79 g, 73%) as a light brown oil. MS m / e: 338.3 [M + H] &lt; ⁺ &gt;.

b) r ac - {(3R , 4S) -4- (3,4- dichloro-phenyl) -1- [1- (1-methyl-cyclopropane car bonil) -piperidine-4-carbonyl] -pyrrolidin-3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester

To a solution of rac - {4 - [(3S, 4R) -3- (3,4-dichloro-phenyl) -4-methylamino-pyrrolidine- 1-carbonyl] -piperidine N, N-diisopropylethylamine (29 l, 0.17 mmol), 4-fluorophenylchloro (4-fluoro-phenyl) Formate (19 L, 0.15 mmol) was added and the resulting mixture was stirred at ambient temperature for 18 hours. This was diluted with EtOAc (15 mL) and washed with an aqueous solution of sodium carbonate (1 M, 10 mL). The aqueous layer was extracted with dichloromethane (30 mL), dried over sodium sulfate and concentrated. Chromatography (SiO _2, heptane: ethyl acetate = 100: 0 to 90:10) to obtain the title compound (45 mg, 68%) was obtained as a light brown oil. MS m / e: 576.3 [M + H] &lt; ⁺ &gt;.

Example  3

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) Cyclopropane carbon Yl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid Cyclopentyl  Ester

Example 2 In analogy to the synthetic procedures described in the (step b), and 4-fluoro instead of phenyl chloroformate using cyclopentyl chloroformate rac - {4 - [(3S , 4R) -3- (3, The title compound, rac - {(3R (4-chloro-phenyl) -4-methylamino-pyrrolidine- 1-carbonyl] -piperidin- , 4S) -4- (3,4-dichloro-phenyl) -l- [l- (1 -methyl- cyclopropanecarbonyl) -piperidine- 4-carbonyl] -pyrrolidin- } -Methyl-carbamic acid cyclopentyl ester as a white solid. MS m / e: 550.3 [M + H] &lt; ⁺ &gt;.

Example  4

rac - [(3R, 4S) -1- (1- Cyclopropylmethyl -Piperidine-4-carbonyl) -4- (3,4-dichloro-phenyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

a) rac - [(3R, 4S) -1- (1- cyclopropylmethyl-piperidine-4-carbonyl) -4- (3,4-dichloro-phenyl) -pyrrolidin-3-yl ] -Methyl - carbamic acid tert-butyl ester

Was prepared in analogy to the synthetic procedure described in example 1 (step f) from l- (l-cyclopropylmethyl) -piperidine instead of l- (l-methyl- cyclopropanecarbonyl) -piperidine- Yl ] -methyl-carbamic acid tert-butyl ester was prepared from rac - [(3R, 4S) -4- (3,4- dichloro- phenyl) -pyrrolidin- rac - [(3R, 4S) -1- (1- cyclopropylmethyl-piperidine-4-carbonyl) -4- (3,4-dichloro-phenyl) -pyrrolidin-3-yl] - Methyl-carbamic acid tert-butyl ester as a brown oil which was used directly in the next step without purification.

b) rac - (1- cyclopropylmethyl-piperidin-4-yl) - [(3S, 4R) -3- (3,4- dichloro-phenyl) -4-methylamino-pyrrolidin -1 - yl] - methane

In analogy to the synthetic procedure described in example 2 (step a), rac - {(3R, 4S) -4- (3,4-dichloro- phenyl) yl) -piperidine-4-carbonyl] -pyrrolidin-3-yl} -methyl-carbamic acid tert-butyl ester in place of rac - [(3R, 4S) -1- (1- cyclopropylmethyl -piperidine-4-carbonyl) -4- (3,4-dichloro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid tert-butyl ester title compound was prepared from rac - (1- 4-methylamino-pyrrolidin-l-yl] -methanone was obtained as a brown solid in brown As an oil. MS m / e: 410.2 [M + H] &lt; ⁺ &gt;.

c) rac - [(3R, 4S) -1- (1- cyclopropylmethyl-piperidine-4-carbonyl) -4- (3,4-dichloro-phenyl) -pyrrolidin-3-yl ] -Methyl - carbamic acid 4- fluoro - phenyl ester

In analogy to the synthetic procedure described in example 2 (step b), rac - {4 - [(3S, 4R) -3- (3,4-Dichloro- phenyl) -4- methylamino-pyrrolidin- - carbonyl] -piperidin-1-yl} - (l-methyl-cyclopropyl) - in place of methane rac - (1-cyclopropylmethyl-piperidin-4-yl) - [(3S, 4R) 3- (3,4-dichloro-phenyl) -4-methylamino-pyrrolidin-1-yl] - methanone The title compound from rac - [(3R, 4S) -1- (1- cyclopropylmethyl- 4-carbonyl) -4- (3,4-dichloro-phenyl) -pyrrolidin-3-yl] -methyl- carbamic acid 4-fluoro-phenyl ester as a pale yellow oil . MS m / e: 548.2 [M + H] &lt; ⁺ &gt;.

Example  5

{(3R, 4S) -4- (3,4-Dichloro-phenyl) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

And

Example  6

{(3S, 4R) -4- (3,4-Dichloro-phenyl) -1- [1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

Rac - {(3R, 4S) -4- (3,4- dichloro-phenyl) -1- [1- (1-cyclopenten one propane-carbonyl) -piperidine-4-carbonyl] -pyrrolidin (3R, 4S) -4- (3,4-Dichloro-phenyl) -l- [l- (MS (m / e)), was prepared in accordance with the general method of example 1 from l- (l-methyl-cyclopropanecarbonyl) -piperidine-4-carbonyl] -pyrrolidin- : 576.2 [M + H] &lt; ⁺ &gt;) as a white foam and {(3S, 4R) -4- (3,4- Fluoro-phenyl ester (MS (m / e): 576.2 [M + H] &lt; ⁺ &gt;) as a white foam .

Example  7

rac - [(3R, 4S) -1- (1- Cyclopropylmethyl -Piperidine-4-carbonyl) -4- (3,4-dichloro-phenyl) - Pyrrolidine -3 days]- methyl - Carbamic acid Phenyl  Ester

{4 - - Example 2 (step b) rac analogy to the described synthesis procedure, using phenyl chloroformate instead of phenyl chloroformate as fluoro [(3S, 4R) -3- ( 3,4- di (1-cyclopropylmethyl-piperidin-1-yl) - (1-methyl-cyclopropyl) -methanone instead of rac- The title compound, rac- [l, 6] naphthyridin-2-ylmethanesulfonamide was prepared from 3- (3,4-dichloro- (3R, 4S) -1- (l-Cyclopropylmethyl-piperidine-4-carbonyl) -4- (3,4- dichloro- phenyl) -pyrrolidin- Lt; / RTI &gt; acid phenyl ester as colorless oil. MS m / e: 530.2 [M] ^&lt; ⁺ & gt ^; .

Example  8

rac - [(3R, 4S) -1- (1- Cyclopropylmethyl -Piperidine-4-carbonyl) -4- (3,4-dichloro-phenyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  p-tolyl ester

In analogy to the synthetic procedure described in example 2 (step b), using p-tolyl chloroformate in place of fluorophenyl chloroformate, rac - {4 - [(3S, 4R) -3- (3,4 -dichloro-phenyl) -4-methylamino-pyrrolidine-1-carbonyl] -piperidin-1-yl} - (l-methyl-cyclopropyl) - in place of methane rac - (1-cyclopropyl The title compound, rac (4-chloro-phenyl) -4-methyl-pyrrolidin- - [(3R, 4S) -l- (l-cyclopropylmethyl-piperidine-4-carbonyl) -4- (3,4- dichloro- phenyl) -pyrrolidin- -Carbamic acid p-tolyl ester as a colorless oil. MS m / e: 544.2 [M] ^&lt; ⁺ & gt ^; .

Example  9

rac - [(3R, 4S) -1- (1- Cyclopropylmethyl -Piperidine-4-carbonyl) -4- (3,4-dichloro-phenyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Methoxy - Phenyl  Ester

Using 4-methoxy-phenyl chloroformate instead of fluorophenyl chloroformate, rac- {4 - [(3S, 4R) -3- ( (1) instead of rac - (1-methyl-phenyl) -4-methylamino-pyrrolidine- 1-carbonyl] -piperidin- - [(3S, 4R) -3- (3,4-dichloro-phenyl) -4-methylamino-pyrrolidin- 1 -yl] -methane The title compound, rac - [(3R, 4S) -1- (1- cyclopropylmethyl-piperidine-4-carbonyl) -4- (3,4-dichloro-phenyl) -pyrrolidin-3-yl ] -Methyl-carbamic acid 4-methoxy-phenyl ester as colorless oil. MS m / e: 560.2 [M] ^&lt; ⁺ & gt ^; .

Example  10

rac - [(3R, 4S) -1- (1- Cyclopropylmethyl -Piperidine-4-carbonyl) -4- (3,4-dichloro-phenyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Chloro - Phenyl  Ester

Using 4-chloro-phenyl chloroformate in place of fluorophenyl chloroformate, rac - {4 - [(3S, 4R) -3- (3 , 4-dichloro-phenyl) -4-methylamino-pyrrolidine-1-carbonyl] -piperidin-1-yl} - (l-methyl-cyclopropyl) - in place of methane rac - (1 Pyrrolidin-l-yl] -methanone was obtained from (3S, 4R) -3- (3,4-dichloro- phenyl) -4-methylamino-pyrrolidin- compound rac - [(3R, 4S) -1- (1- cyclopropylmethyl-piperidine-4-carbonyl) -4- (3,4-dichloro-phenyl) -pyrrolidin-3-yl; -Methyl-carbamic acid 4-chloro-phenyl ester as colorless oil. MS m / e: 564.2 [M] ^&lt; ⁺ & gt ^; .

Example  11

rac - [(3R, 4S) -1- (1- Cyclopropylmethyl -Piperidine-4-carbonyl) -4- (3,4-dichloro-phenyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  Butyl ester

(3S, 4R) -3- (3,4-di (tert-butoxycarbonyl) amino ] propionic acid was prepared in analogy to the synthetic procedure described in example 2 (step b) using butyl chloroformate instead of fluorophenyl chloroformate. (1-cyclopropylmethyl-piperidin-1-yl) - (1-methyl-cyclopropyl) -methanone instead of rac- The title compound, rac- [l, 6] naphthyridin-2-ylmethanesulfonamide was prepared from 3- (3,4-dichloro- (3R, 4S) -1- (l-Cyclopropylmethyl-piperidine-4-carbonyl) -4- (3,4- dichloro- phenyl) -pyrrolidin- Lt; / RTI &gt; acid ethyl ester as a colorless oil. MS m / e: 510.4 [M] ^&lt; ⁺ & gt ^; .

Example  12

rac - {(3R, 4S) -4- (3,4-dichloro-phenyl) -l- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Chloro - Phenyl  Ester

Using 4-chlorophenyl-chloroformate in place of 4-fluorophenyl chloroformate, rac - {4 - [(3S, 4R) -3- (3,4-dichloro-phenyl) -4-methylamino-pyrrolidine-1-carbonyl] -piperidin-1-yl} - (l-methyl-cyclopropyl) - title compound was prepared from methane rac - [(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- 3-yl} -methyl-carbamic acid 4-chloro-phenyl ester as a white foam. MS m / e: 592.3 [M] ^&lt; ⁺ & gt ^; .

Example  13

rac - {(3R, 4S) -4- (3,4-dichloro-phenyl) -l- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid Phenyl  Ester

Using 4-fluorophenyl chloroformate instead of 4-fluorophenyl chloroformate, rac - {4 - [(3S, 4R) -3- (3,4 - {(3R, 5S ) -2-methyl-pyrrolidin-1-ylmethyl) -piperidin- 4-carbonyl] -pyrrolidin-3-yl} - lH-pyrrolo [2,3-c] -Methyl-carbamic acid phenyl ester as a light brown foam. MS m / e: 558.0 [M] ^&lt; ⁺ & gt ^; .

Example  14

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) Cyclopropane carbon Yl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  p-tolyl ester

Example 2 In analogy to the synthetic procedures described in the (step b), using phenyl chloroformate p- tolyl chloroformate in place of 4-fluoro-mate rac - {4 - [(3S , 4R) -3- (3 , 4-dichloro-phenyl) -4-methylamino-pyrrolidine-1-carbonyl] -piperidin-1-yl} - (l-methyl-cyclopropyl) - title compound was prepared from methane rac - {( 3R, 4S) -4- (3,4-Dichloro-phenyl) -l- Yl} -methyl-carbamic acid p-tolyl-phenyl ester as a light brown foam. MS m / e: 572.2 [M] ^&lt; ⁺ & gt ^; .

Example  15

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) Cyclopropane carbon Yl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  p- Methoxyphenyl  Ester

Using 4-fluorophenyl chloroformate instead of 4-fluorophenyl chloroformate, rac - {4 - [(3S, 4R) -3- (3,4-dichloro-phenyl) -4-methylamino-pyrrolidine-1-carbonyl] -piperidin-1-yl} - (l-methyl-cyclopropyl) - title compound was prepared from methane rac - [(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- 3-yl} -methyl-carbamic acid p-methoxy-phenyl ester as a light brown foam. MS m / e: 588.2 [M] ^&lt; ⁺ & gt ^; .

Example  16

{(3R, 4S) -4- (3,4-Dichloro-phenyl) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  p-tolyl ester

And

Example  17

{(3S, 4R) -4- (3,4-Dichloro-phenyl) -1- [1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  p-tolyl ester

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- 3-yl} -methyl-carbamic acid p-tolyl ester was purified by column chromatography on chiral top to give {(3R, 4S) -4- (3,4- (M / e): 572.3 [M] ^&lt; &quot;^& gt ^; ) As an off-white foam and {(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- ] -Pyrrolidin-3-yl} -methyl-carbamic acid p-tolyl ester (MS (m / e): 572.3 [M] ⁺ ) as a colorless oil.

Example  18

{(3R, 4S) -4- (3,4-Dichloro-phenyl) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Chlorophenyl  Ester

And

Example  19

{(3S, 4R) -4- (3,4-Dichloro-phenyl) -1- [1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Chlorophenyl  Ester

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- (3R, 4S) -4- (3,4-Dichloro-phenyl) -l- [l- (M / e): 592.3 &lt; RTI ID = 0.0 &gt; [M &lt; / RTI &gt; ] ⁺ ) Was obtained as off-white foam and {(3S, 4R) -4- (3,4-dichloro-phenyl) Carbonyl] -pyrrolidin-3-yl} -methyl-carbamic acid 4-chlorophenyl ester (MS (m / e): 592.3 [M] ⁺ ) as an off-white foam.

Example  20

 [(3R, 4S) -1- (1-cyclopropyl methyl -Piperidine-4-carbonyl) -4- (3,4-dichloro-phenyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Methoxy - Phenyl  Ester

And

Example  21

[(3S, 4R) -1- (1-cyclopropyl methyl -Piperidine-4-carbonyl) -4- (3,4-dichloro-phenyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Methoxy - Phenyl  Ester

rac - [(3R, 4S) -1- (1- cyclopropylmethyl-piperidine-4-carbonyl) -4- (3,4-dichloro-phenyl) -pyrrolidin-3-yl] - Methyl-carbamic acid 4-methoxy-phenyl ester was chromatographed on a chiral top to give [(3R, 4S) -1- (1-cyclopropylmethyl- piperidine- Methoxy-phenyl ester (MS (m / e): 560.2 [M] ⁺ ) as a colorless oil and [( 3-yl] -methyl-carbamic acid &lt; / RTI &gt;&lt; RTI ID = 0.0 & Methoxy-phenyl ester (MS (m / e): 560.2 [M] <^+> ) as a colorless oil.

Example  22

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) Cyclopropane carbon Yl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  2,2- Dimethyl -Profile ester

Example 2 In analogy to the synthetic procedures described in the (step b), and 4-fluoro instead of phenyl chloroformate using neopentyl chloroformate rac - {4 - [(3S , 4R) -3- (3, The title compound, rac - {(3R (4-chloro-phenyl) -4-methylamino-pyrrolidine- 1-carbonyl] -piperidin- , 4S) -4- (3,4-dichloro-phenyl) -l- [l- (1 -methyl- cyclopropanecarbonyl) -piperidine- 4-carbonyl] -pyrrolidin- } -Methyl-carbamic acid 2,2-dimethyl-propyl ester as a yellow foam. MS m / e: 552.3 [M] ^&lt; ⁺ & gt ^; .

Example  23

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) Cyclopropane carbon Yl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid Professional Yl ester

Example 2 In analogy to the synthetic procedures described in the (step b), using phenyl chloroformate instead of propargyl chloroformate 4-fluoro rac - {4 - [(3S , 4R) -3- (3, The title compound, rac - {(3R (4-chloro-phenyl) -4-methylamino-pyrrolidine- 1-carbonyl] -piperidin- , 4S) -4- (3,4-dichloro-phenyl) -l- [l- (1 -methyl- cyclopropanecarbonyl) -piperidine- 4-carbonyl] -pyrrolidin- } -Methyl-carbamic acid prop-2-ynyl ester as yellow foam. MS m / e: 552.3 [M] ^&lt; ⁺ & gt ^; .

Example  24

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- [l- Cyclopropane carbon Yl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid Cyclopropylmethyl  Ester

To a solution of 1,1'-carbonyl-diimidazole (102 mg, 0.627 mmol) in dioxane (1 mL) was added hydroxymethyl cyclopropane (55 μL, 0.68 mmol). After stirring at ambient temperature for 15 minutes, a solution of rac - {4- [(3S, 4R) -3- (3,4-dichloro- phenyl) -4-methylamino-pyrrolidine- (50 mg, 0.11 mmol) was added and the solution was irradiated with microwave at 170 &lt; 0 &gt; C for 900 seconds and 200 &lt; 0 &gt; C for 1800 seconds. The reaction mixture was diluted with ethyl acetate (15 mL), washed with water (15 mL) and brine (15 mL). The organic layer was extracted with ethyl acetate, dried over sodium sulfate and concentrated. Chromatography (SiO _2, ethyl acetate: methanol = 100: 0 to 85:15) to obtain the title compound (21 mg, 34%) was obtained as a light brown oil. MS m / e: 536.4 [M] ^&lt; ⁺ & gt ^; .

Example  25

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) Cyclopropane carbon Yl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  2- Cyclopropyl - ethyl ester

To a solution of triphosgene (68 mg, 0.23 mmol) in dichloromethane (0.5 mL) was added 2-cyclopropylethanol (69 mg, 0.80 mmol). The solution was stirred at ambient temperature for 45 minutes before N, N-diisopropylethylamine (156 L, 0.912 mmol) and rac- {4- [(3S, 4R) -3- Yl) - (1-methyl-cyclopropyl) -methanone (50 mg, 0.11 mmol) was added to a solution of The solution was stirred at ambient temperature for 3 days. It was diluted with ethyl acetate (15 mL) and washed with aqueous sodium carbonate (1 M, 15 mL) and brine (15 mL). The aqueous layer was extracted with ethyl acetate, dried over sodium sulfate and concentrated. Chromatography to afford the title compound (59 mg, 94%) to give the (SiO _2, ethyl acetate: methanol = 100: 0 to 80:20) as an off-white foam was obtained. MS m / e: 550.3 [M] ^&lt; ⁺ & gt ^; .

Example  26

rac - {(3R, 4S) -4- (4- Chloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

a) rac- (3S, 4R) -l-Benzyl-3- (4 -chloro - phenyl ) -4-nitro- pyrrolidine

Chloro-4 - ((E) - (E) -2-nitro-vinyl) -benzene was prepared in analogy to the synthetic procedure described in example 1 2-nitro-vinyl) benzene the title compound, rac - (3S, 4R) -1- benzyl-3- (4-chloro-phenyl) -4-nitro-pyrrolidine was obtained as a pink oil. MS m / e: 317.1 [M] ^&lt; ⁺ & gt ^; .

b) rac - (3R, 4S ) -1- benzyl-4- (4-chloro-phenyl) -pyrrolidin-3-ylamine

In analogy with the synthesis procedure described in Example 1 (step b), rac - (3R, 4S) -1- benzyl-3- (3,4-dichloro-phenyl) -4-nitro-blood instead of pyrrolidine rac (3R, 4S) -l-benzyl-4- (4-chloro- phenyl) -4-nitro-pyrrolidine was prepared the title compound [ Phenyl) -pyrrolidin-3-ylamine as a light brown oil. MS m / e: 287.1 [M + H] &lt; ⁺ &gt;.

c) rac - [(3R, 4S) -1- benzyl-4- (4-chloro-phenyl) -pyrrolidin-3-yl] -methyl-amine

(3S, 4R) -l-Benzyl-4- (3,4-dichloro-phenyl) -pyrrolidin-3-ylamine instead of rac- rac - (3R, 4S) -1- benzyl-4- (4-chloro-phenyl) -pyrrolidin-3-yl amine The title compound, rac - [(3R, 4S) -1- benzyl-4- (4 -Chloro-phenyl) -pyrrolidin-3-yl] -methyl-amine as colorless oil. MS m / e: 301.2 [M + H] &lt; ⁺ &gt;.

d) rac - [(3R, 4S) -1- benzyl-4- (4-chloro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid tert-butyl ester

In analogy to the synthetic procedure described in example 1 (step d), rac - [(3R, 4S) -l-benzyl- 4- (3,4- dichloro- phenyl) -pyrrolidin- methyl-amine in place of rac - [(3R, 4S) -1- benzyl-4- (4-chloro-phenyl) -pyrrolidin-3-yl] - amine the title compound, rac - - methyl [(3R, 4S ) -L-benzyl-4- (4-chloro-phenyl) -pyrrolidin-3- yl] -methyl- carbamic acid tert- butyl ester as a white foam. MS m / e: 401.3 [M + H] &lt; ⁺ &gt;.

e) rac - [(3R, 4S) -4- (4 -Chloro - phenyl ) -pyrrolidin- 3- yl] -methyl - carbamic acid tert- butyl ester

In analogy with the synthesis procedure described in Example 1 (step e), rac - [(3R , 4S) -1- benzyl-4- (3,4-dichloro-phenyl) -pyrrolidin-3-yl] - Methyl-carbamic acid tert-butyl ester instead of rac - [(3R, 4S) -l-benzyl-4- (4- chloro-phenyl) -pyrrolidin- Butyl ester was obtained as a brown oil from the title compound rac - [(3R, 4S) -4- (4-chloro-phenyl) -pyrrolidin-3- yl] -methyl- carbamic acid tert- butyl ester. MS m / e: 311.2 [M + H] &lt; ⁺ &gt;.

f) rac - {(3R, 4S) -4- (4- chloro-phenyl) -1- [1- (1-cyclopenten one propane-carbonyl) -piperidine-4-carbonyl] -pyrrolidin Yl} -methyl - carbamic acid tert-butyl ester

In analogy to the synthetic procedure described in example 1 (step f), rac - [(3R, 4S) -4- (3,4-dichloro- phenyl) -pyrrolidin- tert-butyl ester in place of rac - [(3R, 4S) -4- (4- chloro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid tert-butyl ester title compound was prepared from rac - { -Piperidin-4-carbonyl] -pyrrolidin-3-yl} - (4-chloro-phenyl) -Methyl-carbamic acid tert-butyl ester as a light brown foam. MS m / e: 504.3 [M] ^&lt; ⁺ & gt ^; .

g) rac - {4 - [(3S, 4R) -3- (4 -Chloro - phenyl ) -4 -methylamino - pyrrolidine- 1-carbonyl] -piperidin- -Methyl - cyclopropyl ) -methanone & lt; / RTI & gt;

In analogy to the synthetic procedure described in example 2 (step a), rac - {(3R, 4S) -4- (3,4-dichloro- phenyl) yl) -piperidine-4-carbonyl] -pyrrolidin-3-yl} -methyl-carbamic acid tert-butyl ester in place of rac - {(3R, 4S) -4- (4- chloro-phenyl Yl} -methyl-carbamic acid tert-butyl ester was prepared the title compound rac (1S) from rac-5-dihydro- Yl) - (1-methyl-pyridin-2-yl) - (4- Cyclopropyl) -methanone as a light brown foam. MS m / e: 404.4 [M + H] &lt; ⁺ &gt;.

h) rac - {(3R, 4S) -4- (4- chloro-phenyl) -1- [1- (1-cyclopenten one propane-carbonyl) -piperidine-4-carbonyl] -pyrrolidin Yl} -methyl - carbamic acid 4- fluoro - phenyl ester

In analogy to the synthetic procedure described in example 2 (step b), rac - {4 - [(3S, 4R) -3- (3,4-Dichloro- phenyl) -4- methylamino-pyrrolidin- - carbonyl] -piperidin-1-yl} - (l-methyl-cyclopropyl) - in place of methane rac - {4 - [(3S , 4R) -3- (4- chloro-phenyl) -4 methylamino-pyrrolidine-1-carbonyl] -piperidin-1-yl} - (l-methyl-cyclopropyl) - title compound was prepared from methane rac - {(3R, 4S) -4- (4- chloro - phenyl) -l- [l- (1 -methyl-cyclopropanecarbonyl) -piperidine-4- carbonyl] -pyrrolidin-3- yl} -methyl- carbamic acid 4- fluoro-phenyl ester &Lt; / RTI &gt; as a pale yellow foam. MS m / e: 542.3 [M] ^&lt; ⁺ & gt ^; .

Example  27

rac - {(3R, 4S) -4- (4- Chloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  Butyl ester

Example 2 In analogy to the synthetic procedures described in the (step b), 4-fluoro-phenyl chloroformate in place of the tert-butyl chloroformate rac - {4 - [(3S , 4R) -3- (3, 4-chloro-phenyl) -4-methylamino-pyrrolidine-1-carbonyl] -piperidin-1-yl} - (l-methyl-cyclopropyl) - in place of methane rac - {4- [ (L-methyl-cyclopropyl) -methanone was prepared from (lS, 4R) -3- (4-chloro-phenyl) -4-methylamino-pyrrolidine- The title compound from rac - {(3R, 4S) -4- (4- chloro-phenyl) -1- [1- (1-cyclopenten one propane-carbonyl) -piperidine-4-carbonyl] -pyrrolidin Pyridin-3-yl} -methyl-carbamic acid butyl ester as a light yellow foam. MS m / e: 504.2 [M] ^&lt; ⁺ & gt ^; .

Example  28

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  6- Chloro -Pyridin-3-yl ester

In analogy to the synthetic procedure described in example 25, 2- chloro- 5-hydroxypyridine was used instead of 2-cyclopropylethanol to give rac- {4 - [(3S, 4R) -3- chloro-phenyl) -4-methylamino-pyrrolidine-1-carbonyl] -piperidin-1-yl} - (l-methyl-cyclopropyl) - title compound was prepared from methane rac - {(3R, 4S) -Piperidin-4-carbonyl] -pyrrolidin-3-yl} -methyl- [l- -Carbamic acid 6-chloro-pyridin-3-yl ester as a light brown foam. MS m / e: 593.2 [M] ^&lt; ⁺ & gt ^; .

Example  29

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- [l- Cyclopropane carbon Yl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  3,3,3- Trifluro -Profile ester

Example In analogy to the procedure described in Synthesis 25, using 1-propanol instead of 3,3,3-trifluoro-2-cyclopropyl-ethanol rac - {4 - [(3S , 4R) -3- (3 , 4-dichloro-phenyl) -4-methylamino-pyrrolidine-1-carbonyl] -piperidin-1-yl} - (l-methyl-cyclopropyl) - title compound was prepared from methane rac - {( 3R, 4S) -4- (3,4-Dichloro-phenyl) -l- Yl} methyl-carbamic acid 3,3,3-trifluoro-propyl ester as a yellow foam. MS m / e: 578.2 [M] ^&lt; ⁺ & gt ^; .

Example  30

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  3,3- Dimethyl - butyl ester

Example In analogy to the procedure described in Synthesis 25, using 3,3-dimethyl-1-butanol in place of 2-cyclopropyl ethanol rac - {4 - [(3S , 4R) -3- (3,4- dichloro-phenyl) -4-methylamino-pyrrolidine-1-carbonyl] -piperidin-1-yl} - (l-methyl-cyclopropyl) - title compound was prepared from methane rac - {(3R, 4S Yl) -piperidin-4-carbonyl] -pyrrolidin-3-yl} - (4- Methyl-carbamic acid 3,3-dimethyl-butyl ester as a light yellow foam. MS m / e: 566.3 [M] ^&lt; ⁺ & gt ^; .

Example  31

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid Tetrahydro -Pyran-4- Ime Tylester

In analogy with the synthesis procedure described in Example 25, using 2-cyclopropyl-tetrahydro -2H- pyran-4-yl methanol in place of ethanol rac - {4 - [(3S , 4R) -3- (3,4 -dichloro-phenyl) -4-methylamino-pyrrolidine-1-carbonyl] -piperidin-1-yl} - (l-methyl-cyclopropyl) - title compound was prepared from methane rac - {(3R, 4-carbonyl] -pyrrolidin-3-yl} - lH-pyrrolo [2,3-c] -Methyl-carbamic acid tetrahydro-pyran-4-ylmethyl ester as a pale yellow foam. MS m / e: 580.2 [M] ^&lt; ⁺ & gt ^; .

Example  32

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid Cyclopentylmethyl  Ester

4- (3S, 4R) -3- (3,4-Dichloro-phenyl) -4H-pyrrolo [2,3-d ] pyrimidine-3- carboxylic acid ethyl ester in analogy to the synthetic procedure described in example 25, using cyclopentanemethanol instead of 2- -methylamino-pyrrolidine-1-carbonyl] -piperidin-1-yl} - (l-methyl-cyclopropyl) - title compound was prepared from methane rac - {(3R, 4S) -4- (3, 4-carbonyl] -pyrrolidin-3-yl} -methyl-carbamic acid cyclopentylmethyl (2-methyl-piperazin-1- Ester as a pale yellow foam. MS m / e: 566.3 [M] ^&lt; ⁺ & gt ^; .

Example  33

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- [l- Cyclopropane carbon Yl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  3- methyl - Oxetane -3- Yl methyl  Ester

In analogy to the synthetic procedure described in example 25, 3-methyl-3-oxetanemethanol was used instead of 2-cyclopropylethanol to give rac- {4 - [(3S, 4R) -3- chloro-phenyl) -4-methylamino-pyrrolidine-1-carbonyl] -piperidin-1-yl} - (l-methyl-cyclopropyl) - title compound was prepared from methane rac - {(3R, 4S) -Piperidin-4-carbonyl] -pyrrolidin-3-yl} -methyl- [l- -Carbamic acid 3-methyl-oxetan-3-ylmethyl ester as a light yellow foam. MS m / e: 566.5 [M] ^&lt; ⁺ & gt ^; .

Example  34

rac - {(3R, 4S) -4- (3,4- Dichloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  6- Trifluoromethyl -Pyridin-3-yl ester

Example In analogy to the procedure described in Synthesis 25, using 2-cyclopropyl-6- (trifluoromethyl) pyridin-3-ol in ethanol instead of rac - {4 - [(3S , 4R) -3- (3 -Acetic acid was prepared from rac - {(4-chloro-phenyl) -4-methylamino-pyrrolidine- 1-carbonyl] -piperidin- (3R, 4S) -4- (3,4-Dichloro-phenyl) -l- -Yl} -methyl-carbamic acid 6-trifluoromethyl-pyridin-3-yl ester as a light brown oil. MS m / e: 627.2 [M] ^&lt; ⁺ & gt ^; .

Example  35

{(3R, 4S) -4- (3,4- Dichloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidin-4- Ahborn ] - Pyrrolidine -3 days}- methyl - Carbamic acid  2- Cyclopropyl - ethyl ester

And

Example  36

{(3S, 4R) -4- (3,4- Dichloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidin-4- Ahborn ] - Pyrrolidine -3 days}- methyl - Carbamic acid  2- Cyclopropyl - ethyl ester

rac - [(3R, 4S) -1- (1- cyclopropylmethyl-piperidine-4-carbonyl) -4- (3,4-dichloro-phenyl) -pyrrolidin-3-yl] - Methyl-carbamic acid 2-cyclopropyl-ethyl ester was subjected to column chromatography on chiral top to give [(3R, 4S) -1- (1-cyclopropylmethyl- piperidine- Methyl) -carbamic acid 2-cyclopropyl-ethyl ester (MS (m / e): 550.3 [M] <^+> ) as a light brown oil and [( 3-yl] -methyl-carbamic acid &lt; / RTI &gt;&lt; RTI ID = 0.0 & 2-Cyclopropyl-ethyl ester (MS (m / e): 550.3 [M] ⁺ ) was obtained as a light brown oil.

Example  37

rac - [(3R, 4S) -4- (3,4- Dichloro - Phenyl )-One-( The trans- 4- Hydroxy - Cyclohexanecarbonyl ) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

a) rac - [(3R, 4S) -1- benzyl-4- (3,4-dichloro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester

In analogy to the synthetic procedure described in example 2 (step b), rac - {4 - [(3S, 4R) -3- (3,4-Dichloro- phenyl) -4- methylamino-pyrrolidin- - carbonyl] -piperidin-1-yl} - (l-methyl-cyclopropyl) -methanone in place of rac - [(3S, 4R) -1-benzyl-4- (3,4- phenyl) -pyrrolidin-3-yl] -methyl-amine The title compound, rac - [(3R, 4S) -1- benzyl-4- (3,4-dichloro-phenyl) -pyrrolidin-3 Yl] -methyl-carbamic acid 4-fluoro-phenyl ester as colorless oil. MS m / e: 473.1 [MH] ^&lt; ^{+ &} gt ;.

b) rac - [(3R, 4S) -4- (3,4- dichloro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester

In analogy with the synthesis procedure described in Example 1 (step e), rac - [(3R , 4S) -1- benzyl-4- (3,4-dichloro-phenyl) -pyrrolidin-3-yl] - (3R, 4S) -l-benzyl-4- (3,4-dichloro-phenyl) -pyrrolidin-3- yl] -methyl- carbamic acid tert- butyl ester in place of rac - [ The title compound, rac - [(3R, 4S) -4- (3,4-dichloro-phenyl) -pyrrolidin-3- yl] -methyl-carbamic acid 4-fluoro- Phenyl ester as a light brown foam. MS m / e: 383.1 [M] ^&lt; ⁺ & gt ^; .

c) rac - [(3R, 4S) -4- (3,4- dichloro-phenyl) -1- (trans-4-hydroxy-yl cyclohexane-carbonyl) -pyrrolidin-3-yl] -methyl -carbamic acid 4-fluoro-phenyl ester

Example 1 (step f) In analogy to the synthetic procedure described in 1- (1-methyl-cyclopropane-carbonyl) -piperidine-4-carboxylic acid in place of trans-using 4-hydroxy-cyclohexanecarboxylic acid rac - [(3R, 4S) -4- (3,4- dichloro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid tert-butyl ester in place of rac - [(3R, 4S) - The title compound, rac - [(3R, 4S) -4- (3, 5-difluoro-phenyl) -pyrrolidin- 4-dichloro-phenyl) -1- (trans-4-hydroxy-cyclohexane-carbonyl) -pyrrolidin-3-yl] - carbamic acid with 4-fluoro-phenyl methyl ester as a light brown oil . MS m / e: 509.3 [M] ^&lt; ⁺ & gt ^; .

Example  38

{(3R, 4S) -4- (4- Chloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

And

Example  39

{(3S, 4R) -4- (4- Chloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

rac - {(3R, 4S) -4- (4-Chloro-phenyl) -l- Yl} -methyl-carbamic acid 4-fluoro-phenyl ester was chromatographed on a chiral top to give {(3R, 4S) -4- -cyclopropane-carbonyl) -piperidine-4-carbonyl] -pyrrolidin-3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester (MS (m / e): 542.2 [m] + ) As a white foam and {(3S, 4R) -4- (4-chloro-phenyl) -l- Yl) -methyl-carbamic acid 4-fluoro-phenyl ester (MS (m / e): 542.2 [M] <^+> ) as a white foam.

Example  40

rac - {(3R, 4R) -4- (3,4- Dichloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

a) rac - [(3R, 4R) -1- benzyl-4- (3,4-dichloro-phenyl) -pyrrolidin-3-yl] -methyl-amine

(3S, 4R) -l-Benzyl-4- (3,4-dichloro-phenyl) -pyrrolidin-3-ylamine instead of rac- The title compound, rac - [(3R, 4R) -l-benzyl-4-methyl-lH-pyrrolo [ - (3,4-dichloro-phenyl) -pyrrolidin-3-yl] -methyl-amine as a light brown oil. MS m / e: 335.2 [M] &lt; ⁺ & gt ^; .

b) rac - [(3R, 4R) -1- benzyl-4- (3,4-dichloro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid tert-butyl ester

In analogy to the synthetic procedure described in example 1 (step d), rac - [(3R, 4S) -l-benzyl- 4- (3,4- dichloro- phenyl) -pyrrolidin- Yl] -methyl-amine instead of rac - [(3R, 4R) -l-benzyl-4- (3,4-dichloro- phenyl) -pyrrolidin- 3R, 4R) - l- benzyl-4- (3,4-dichloro-phenyl) -pyrrolidin-3- yl] -methyl- carbamic acid tert- butyl ester as light brown oil. MS m / e: 435.2 [M] ^&lt; ⁺ & gt ^; .

c) rac - [(3R, 4R) -4- (3,4 -Dichloro - phenyl ) -pyrrolidin- 3- yl] -methyl - carbamic acid tert- butyl ester

In analogy with the synthesis procedure described in Example 1 (step e), rac - [(3R , 4S) -1- benzyl-4- (3,4-dichloro-phenyl) -pyrrolidin-3-yl] - (3R, 4R) -l-Benzyl-4- (3,4-dichloro-phenyl) -pyrrolidin-3- yl] -methyl- carbamic acid tert- butyl ester in place of rac - [ The title compound, rac - [(3R, 4R) -4- (3,4-dichloro-phenyl) -pyrrolidin-3- yl] -methyl-carbamic acid tert- butyl ester was obtained from brown As an oil. MS m / e: 345.1 [M] &lt; ⁺ & gt ^; .

d) rac - {(3R, 4R) -4- (3,4- dichloro-phenyl) -1- [1- (1-methyl-cyclopropane-carbonyl) -piperidine-4-carbonyl] - Pyrrolidin- 3 - yl} -methyl - carbamic acid tert-butyl ester

In analogy to the synthetic procedure described in example 1 (step f), rac - [(3R, 4S) -4- (3,4-dichloro- phenyl) -pyrrolidin- The title compound, was prepared from rac - [(3R, 4RS) -4- (3,4-dichloro-phenyl) -pyrrolidin-3- yl] -methyl-carbamic acid tert- butyl ester in lieu of tert- rac - {(3R, 4R) -4- (3,4-Dichloro-phenyl) Pyridin-3-yl} -methyl-carbamic acid tert-butyl ester as a brown oil. MS m / e: 538.3 [M] ^&lt; ⁺ & gt ^; .

e) rac - {4 - [ (3R, 4R) -3- (3,4- dichloro-phenyl) -4-methylamino-pyrrolidin-1-yl-carbonyl] - piperidin-1-yl} - (1- methyl - cyclopropyl ) -methanone

In analogy to the synthetic procedure described in example 2 (step a), rac - {(3R, 4S) -4- (3,4-dichloro- phenyl) yl) -piperidine-4-carbonyl] -pyrrolidin-3-yl} -methyl-carbamic acid tert-butyl ester in place of rac - {(3R, 4R) -4- (3,4- dimethyl 3-yl} -methyl-carbamic acid tert-butyl ester as a light yellow solid, MS (ISP): m.p. The title compound, rac- {4 - [(3R, 4R) -3- (3,4-Dichloro- phenyl) -4-methylamino- pyrrolidine- 1- carbonyll- piperidin- - (1-methyl-cyclopropyl) -methanone as a brown oil. MS m / e: 438.2 [M] ^&lt; ⁺ & gt ^; .

f) rac - {(3R, 4R) -4- (3,4- dichloro-phenyl) -1- [1- (1-methyl-cyclopropane-carbonyl) -piperidine-4-carbonyl] - Pyrrolidin- 3 - yl} -methyl - carbamic acid 4- fluoro - phenyl ester

In analogy to the synthetic procedure described in example 2 (step b), rac - {4 - [(3S, 4R) -3- (3,4-Dichloro- phenyl) -4- methylamino-pyrrolidin- - carbonyl] -piperidin-1-yl} - (l-methyl-cyclopropyl) -methanone in place of rac - {4 - [(3R , 4R) -3- (3,4- dichloro-phenyl - (3R, 4R) -4-methyl-pyrrolidine-l- carbonyl] -piperidin- 1 -yl} - - (3,4-dichloro-phenyl) -l- [l- (1 -methyl- cyclopropanecarbonyl) -piperidine-4- carbonyl] -pyrrolidin-3- yl} 4-fluoro-phenyl ester as a brown oil. MS m / e: 576.3 [M + H] &lt; ⁺ &gt;.

Example  41

{(3R, 4S) -4- (3,4- Dichloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  6- Chloro -Pyridin-3-yl ester

And

Example  42

{(3S, 4R) -4- (3,4- Dichloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  6- Chloro -Pyridin-3-yl ester

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- (3R, 4S) -4- (3,4-dichloro-phenyl) - &lt; RTI ID = 0.0 & Pyrrolidin-3-yl} -methyl-carbamic acid 6-chloro-pyridin-3-yl ester (prepared from 1- MS (m / e): 593.2 [M] <^+> ) as an off-white foam and {(3S, 4R) -4- (3,4- Methyl) -carbamic acid 6-chloro-pyridin-3-yl ester (MS (m / e): 593.2 [M] ^&lt; ⁺ & gt ^; ) As an off-white foam.

Example  43

rac - {(3R, 4S) -4- (3,4- Dichloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- Carbamic acid  4- Fluoro - Phenyl  Ester

a) rac - [(3R, 4S) -1- benzyl-4- (3,4-dichloro-phenyl) -pyrrolidin-3-yl] -carbamic acid tert-butyl ester

To a solution of rac- (3S, 4R) -l-benzyl-4- (3,4-dichloro-phenyl) -pyrrolidin-3-ylamine (30.64 g, 0.095 mol) in dichloromethane Was added N, N-diisopropylethylamine (32.65 mL, 0.191 mol) and 4-dimethylaminopyridine (1.17 g, 0.010 mol). The reaction mixture was cooled to 0 C and di-tert-butyl-dicarbonate (24.98 g; 0.114 mol) was added in two portions. After stirring at this temperature for 2 hours, the solution was stirred at ambient temperature for 18 hours. Concentrate the resulting mixture, chromatography to afford the (SiO _2, heptane-ethyl acetate = 75: 25) to obtain the title compound (5.82 g, 14%) as a light yellow solid. MS m / e: 421.1 [M] ^&lt; ⁺ & gt ^; .

b) rac - [(3R, 4S) -4- (3,4 -Dichloro - phenyl ) -pyrrolidin- 3- yl] -carbamic acid tert- butyl ester

In analogy with the synthesis procedure described in Example 1 (step e), rac - [(3R , 4S) -1- benzyl-4- (3,4-dichloro-phenyl) -pyrrolidin-3-yl] - methyl-carbamic acid tert-butyl ester in place of rac - [(3R, 4S) -1- benzyl-4- (3,4-dichloro-phenyl) -pyrrolidin-3-yl] -carbamic acid tert -Pyrrolidin-3-yl] -carbamic acid tert-butyl ester as a light brown solid, MS (ISP): m / e = . MS m / e: 331.1 [M + H] &lt; ⁺ &gt;.

c) rac - {(3R, 4S) -4- (3,4- dichloro-phenyl) -1- [1- (1-methyl-cyclopropane-carbonyl) -piperidine-4-carbonyl] - Pyrrolidin- 3 - yl} -carbamic acid tert-butyl ester

In analogy to the synthetic procedure described in example 1 (step f), rac - [(3R, 4S) -4- (3,4-dichloro- phenyl) -pyrrolidin- tert-butyl ester in place of rac - [(3R, 4S) -4- (3,4- dichloro-phenyl) -pyrrolidin-3-yl] -carbamic acid tert-butyl ester title compound was prepared from rac - [(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- 3-yl} -carbamic acid tert-butyl ester as a light brown foam. MS m / e: 524.1 [M] ^&lt; ⁺ & gt ^; .

d) rac - {4 - [ (3R, 4S) -3- amino-4- (3,4-dichloro-phenyl) -pyrrolidine-l-carbonyl] - piperidin-1-yl} - (L- methyl - cyclopropyl ) -methanone

In analogy to the synthetic procedure described in example 2 (step a), rac - {(3R, 4S) -4- (3,4-dichloro- phenyl) yl) -piperidine-4-carbonyl] -pyrrolidin-3-yl} -methyl-carbamic acid tert-butyl ester in place of rac - {(3R, 4S) -4- (3,4- dimethyl Pyrrolidin-3-yl} -carbamic acid tert-butyl ester as starting materials, the title compound, MS: m / e = rac - {4 - [(3R , 4S) -3- amino-4- (3,4-dichloro-phenyl) -pyrrolidine-1-carbonyl] -piperidin-1-yl} - (1 -Methyl-cyclopropyl) -methanone as a light brown foam. MS m / e: 424.2 [M + H] &lt; ⁺ &gt;.

e) rac - {(3R, 4S) -4- (3,4- dichloro-phenyl) -1- [1- (1-methyl-cyclopropane-carbonyl) -piperidine-4-carbonyl] - Pyrrolidin- 3 - yl} -carbamic acid 4- fluoro - phenyl ester

In analogy to the synthetic procedure described in example 2 (step b), rac - {4 - [(3S, 4R) -3- (3,4-Dichloro- phenyl) -4- methylamino-pyrrolidin- - carbonyl] -piperidin-1-yl} - (l-methyl-cyclopropyl) -methanone in place of rac - {4 - [(3R , 4S) -3- amino-4- (3, dichloro-phenyl) -pyrrolidine-1-carbonyl] -piperidin-1-yl} - (l-methyl-cyclopropyl) - methanone The title compound from rac - {(3R, 4S) -4- -Pyrrolidin-3-yl} -carbamic acid 4- (4-chloro-phenyl) -l- Fluoro-phenyl ester as a pale yellow foam. MS m / e: 562.0 [M] ^&lt; ⁺ & gt ^; .

Example  44

rac - [(3R, 4S) -4- (3,4- Dichloro - Phenyl )-One-( Tetrahydro -Pyran-4-carbonyl) -pyrrolidin-3-yl] - methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

a) rac - (3R, 4S ) -1- benzyl-4- (3,4-dichloro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester

In analogy to the synthetic procedure described in example 2 (step b), rac - {4 - [(3S, 4R) -3- (3,4-Dichloro- phenyl) -4- methylamino-pyrrolidin- - carbonyl] -piperidin-1-yl} - (l-methyl-cyclopropyl) -methanone in place of rac - [(3S, 4R) -1-benzyl-4- (3,4- phenyl) -pyrrolidin-3-yl] -methyl-amine The title compound, rac - (3R, 4S) -1- benzyl-4- (3,4-dichloro-phenyl) -pyrrolidin-3-yl ] -Methyl-carbamic acid 4-fluoro-phenyl ester as a colorless oil. MS m / e: 473.1 [M] ^&lt; ⁺ & gt ^; .

b) rac - [(3R, 4S) -4- (3,4- dichloro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester

In analogy with the synthesis procedure described in Example 1 (step e), rac - [(3R , 4S) -1- benzyl-4- (3,4-dichloro-phenyl) -pyrrolidin-3-yl] - methyl-carbamic acid tert-butyl ester in place of rac - (3R, 4S) -1- benzyl-4- (3,4-dichloro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4 Fluoro-phenyl ester was prepared the title compound, rac - [(3R, 4S) -4- (3,4-dichloro- phenyl) -pyrrolidin- Ester as a light brown foam. MS m / e: 383.1 [M] ^&lt; ⁺ & gt ^; .

c) rac - [(3R, 4S) 4- (3,4- dichloro-phenyl) -1- (tetrahydropyran-4-carbonyl) pyrrolidin-3-yl] -methyl-carbamic acid 4 - fluoro - phenyl ester

To a solution of tetrahydropyran-4-yl-carboxylic acid (51 mg, 0.39 mmol) in DMF (1 mL) at ambient temperature was added 2- (lH-benzotriazol- l-yl) -1,1,3,3- Methyl uronium tetrafluoroborate (114 mg, 0.36 mmol) and N, N-diisopropylethylamine (125 mg, 0.97 mmol) were added. After stirring at this temperature for 15 minutes, a solution of rac - [(3R, 4S) -4- (3,4-dichloro-phenyl) -pyrrolidin- A solution of 4-fluoro-phenyl ester (124 mg, 0.32 mol) was added and stirred at ambient temperature for 20 hours. The reaction mixture was diluted with ethyl acetate (10 mL) and washed with aqueous sodium carbonate (1 M, 10 mL), water (10 mL) and brine (10 mL). The aqueous layer was extracted with ethyl acetate (10 mL) and the combined organic layers were dried over sodium sulfate and concentrated. Purification by chromatography (SiO _2, ethyl acetate: methanol = 98: 2 to 85:15) to give the title compound (92 mg, 57%) as a white oil. MS m / e: 495.3 [M] ^&lt; ⁺ & gt ^; .

Example  45

[(3R, 4S) -4- (3,4- Dichloro - Phenyl )-One-( The trans- 4- Hydroxy - Cyclohexanecarbonyl ) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

And

Example  46

[(3S, 4R) -4- (3,4- Dichloro - Phenyl )-One-( The trans- 4- Hydroxy - Cyclohexanecarbonyl ) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

rac - [(3R, 4S) -4- (3,4- dichloro-phenyl) -1- (trans-4-hydroxy-yl cyclohexane-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic Fluoro-phenyl ester was treated by column chromatography on chiral top to give [(3R, 4S) -4- (3,4-dichloro-phenyl) -l- ( trans- Methyl) -carbamic acid 4-fluoro-phenyl ester (MS (m / e): 509.3 [M] ⁺ ) - (3,4-dichloro-phenyl) -1- (trans-4-hydroxy-cyclohexane-carbonyl) -pyrrolidin-3-yl] - carbamic acid with 4-fluoro-phenyl-methyl ester (MS (m / e): 509.3 [M] ^&lt; ⁺ & gt ^; ) as an off-white foam.

Example  47

rac - [(3R, 4S) -4- (3,4- Dichloro - Phenyl )-One-( Cis - 4- Hydroxy - Cyclohexanecarbonyl ) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

Example 44 In analogy to the synthetic procedures described in the (step c), 1- methyl-1-cyclopropane carboxylic acid in place of cis-4-hydroxycyclohexyl using hexane-carboxylic acid rac - {4 - [(3S , 4R) - (L-methyl-cyclopropyl) -methanone was prepared in accordance with the general method of example 1 from 3- (3,4-dichloro-phenyl) -4-methylamino-pyrrolidine- 1- carbonyll- piperidin- The title compound, rac - [(3R) - [(3R, 4R) -4- (3,4- dichloro- phenyl) -pyrrolidin- , 4S) -4- (3,4- dichloro-phenyl) -1- (cis-a carbamic acid 4-fluoro-4-hydroxy-cyclohexane-carbonyl) -pyrrolidin-3-yl] -methyl -Phenyl &lt; / RTI &gt; ester as an off-white foam. MS m / e: 509.2 [M] ^&lt; ⁺ & gt ^; .

Example  48

rac - [(3R, 4S) -4- (3,4- Dichloro - Phenyl )-One-( Morpholine Carbonyl) - Pyrrolidine Yl] -methyl- Carbamic acid  4- Fluoro - Phenyl  Ester

4-carbonyl chloride was used in place of fluorophenyl chloroformate to give rac - {4 - [(3S, 4R) -3- (3 , 4-dichloro-phenyl) -4-methylamino-pyrrolidine-1-carbonyl] -piperidin-1-yl} - (l-methyl-cyclopropyl) -methanone in place of rac - [( The title compound, rac - [(3R, 4S) - (4-chloro-phenyl) -pyrrolidin- 4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester was prepared from 4- (3,4- As a colorless oil. MS m / e: 496.2 [M] ^&lt; ⁺ & gt ^; .

Example  49

rac - [(3R, 4S) -4- (3,4- Dichloro - Phenyl )-One-( Cis - 4- Methoxy - Cyclohexanecarbonyl ) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

Example 44 In analogy to the synthetic procedures described in the (step c), 1- methyl-1-cyclopropane carboxylic acid in place of cis-4-methoxy-cyclo-hexane-carboxylic acid using rac - {4 - [(3S , 4R) - (L-methyl-cyclopropyl) -methanone was prepared in accordance with the general method of example 1 from 3- (3,4-dichloro-phenyl) -4-methylamino-pyrrolidine- 1- carbonyll- piperidin- The title compound, rac - [(3R) - [(3R, 4R) -4- (3,4- dichloro- phenyl) -pyrrolidin- , 4S) -4- (3,4-Dichloro-phenyl) -l- ( cis - 4-methoxy- cyclohexanecarbonyl) -pyrrolidin- 3- yl] -methyl- carbamic acid 4- fluoro -Phenyl &lt; / RTI &gt; ester as a pale yellow oil. MS m / e: 523.4 [M] ^&lt; ⁺ & gt ^; .

Example  50

[(3R, 4S) -4- (3,4- Dichloro - Phenyl )-One-( Tetrahydro -Pyran-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

And

Example  51

[(3S, 4R) -4- (3,4- Dichloro - Phenyl )-One-( Tetrahydro -Pyran-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4 &lt; RTI ID = 0.0 &gt; - fluoro-phenyl ester was subjected to column chromatography on a chiral top to give [(3R, 4S) -4- (3,4-dichloro-phenyl) -l- (tetrahydro- 3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester (MS (m / e): 495.2 [m] +) a as an off-white foam and [(3S, 4R) -4- ( 3, (MS (m / e) &lt; / RTI &gt;:&lt; RTI ID = 0.0 &gt; 495.2 [M] ^&lt; ⁺ & gt ^; ) as an off-white foam.

Example  52

rac - [(3R, 4S) -4- (3,4- Dichloro - Phenyl )-One-( The trans- 4- Hydroxy -4- methyl - Cyclohexanecarbonyl ) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

4-methyl-cyclohexanecarboxylic acid was used in place of 1-methylcyclopropane-l-carboxylic acid to give rac- {4 - [( Yl) - (1-methyl-cyclopropyl) -lH-pyrrolo [2,3-d] pyrimidin- -Pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester instead of rac - [(3R, 4S) -4- ( trans- 4-hydroxy-4-methyl-cyclohexanecarbonyl) -pyrrolidin-3-yl] -Methyl-carbamic acid 4-fluoro-phenyl ester as an off-white foam. MS m / e: 523.3 [M] &lt; ^{+ &} gt ^; .

Example  53

rac - [(3R, 4S) -4- (3,4- Dichloro - Phenyl )-One-( Cis - 4- Hydroxy -4- methyl - Cyclohexanecarbonyl ) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

4-methyl-cyclohexanecarboxylic acid was used in place of 1-methylcyclopropane-l-carboxylic acid in analogy to the synthetic procedure described in example 44 (step c) to give rac- {4 - [ Yl) - (1-methyl-cyclopropyl) -lH-pyrrolo [2,3-d] pyrimidin- -Pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester instead of rac - [(3R, 4S) -4- rac - [(3R, 4S) -4- (3,4- dichloro-phenyl) -1- (cis-4-hydroxy-4-methyl-cyclohexane-carbonyl) -pyrrolidin-3-yl; -Methyl-carbamic acid 4-fluoro-phenyl ester as an off-white foam. MS m / e: 523.3 [M] &lt; ^{+ &} gt ^; .

Example  54

rac - {(3R, 4S) -4- (4- Chloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  2- Cyclopropyl - ethyl ester

In analogy with the synthesis procedure described in example 25, rac - {4 - [ (3S, 4R) -3- (3,4- dichloro-phenyl) -4-methylamino-pyrrolidine-1-carbonyl] (4S, 4R) -3- (4-chloro-phenyl) -4-methylamino-pyrrolidine instead of rac - {4- pyrrolidine-1-carbonyl] -piperidin-1-yl} - (l-methyl-cyclopropyl) - methanone The title compound from rac - {(3R, 4S) -4- (4- chloro-phenyl Pyrrolidin-3-yl} -methyl-carbamic acid 2-cyclopropyl-ethyl ester as an off-white color As a foam. MS m / e: 516.3 [M] ^&lt; ⁺ & gt ^; .

Example  55

rac - [(3R, 4S) -1- (3- carbamoyl-propionyl) -4- (3,4-dichloro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro -phenyl ester

4- (3S, 4R) -3- (3,4- dichloropyrimidin -4-yl) -methanone using succinamic acid instead of 1-methylcyclopropane-1-carboxylic acid in analogy to the synthetic procedure described in example 44 dichloro-phenyl) -4-methylamino-pyrrolidine-1-carbonyl] -piperidin-1-yl} - (l-methyl-cyclopropyl) -methanone in place of rac - [(3R, 4S Yl) - methyl-carbamic acid 4-fluoro-phenyl ester there was obtained the title compound rac - [(3R, 4S) -1- (3-carbamoyl-propionyl) -4- (3,4-dichloro-phenyl) -pyrrolidin-3- yl] -methyl- carbamic acid 4-fluoro-phenyl ester as colorless oil. MS m / e: 465.1 [M] ^&lt; ⁺ & gt ^; .

Example  56

rac - {(3R, 4S) -4- (3,4- Dichloro - Phenyl ) -1- [3- (2-oxo- Pyrrolidine -1 day)- Propionate ] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

In analogy to the synthetic procedure described in example 44 (step c), rac - {4- (2-oxo-pyrrolidin-l-yl) -propionic acid was used in place of 1- methylcyclopropane- - (1-methyl-pyridin-2-ylmethyl) -piperidine-l- Yl) -methyl-carbamic acid 4-fluoro-phenyl ester (prepared according to the procedure described for the synthesis of example 1, step 2c) using rac - [(3R, To give the title compound rac - {(3R, 4S) -4- (3,4-dichloro-phenyl) -l- [3- (2- oxo-pyrrolidin- l-yl) -propionyl] Pyridin-3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester as colorless oil. MS m / e: 522.2 [M] ^&lt; ⁺ & gt ^; .

Example  57

rac - {(3R, 4S) -4- (4- Chloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- methyl - Cyclohexyl  Ester

4-methyl-cyclohexanol was used in place of 2-cyclopropylethanol in analogy to the synthetic procedure described in example 25 to yield rac- {4 - [(3S, 4R) -3- - {4 - [(3S, 5R ) -l- (4-methylpiperidin-l- (4-chloro-phenyl) -4-methylamino-pyrrolidine- 1-carbonyl] -piperidin- 1 -yl} - The title compound, rac - {(3R, 4S) -4- (4-chloro-phenyl) -l- Yl} -methyl-carbamic acid 4-methyl-cyclohexyl ester as an off-white foam. MS m / e: 544.3 [M] ^&lt; ⁺ & gt ^; .

Example  58

rac -1 - {(3R, 4S) -4- (4- Chloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine Yl} -3- (2- Cyclopropyl -Ethyl) -1- methyl - Urea

In analogy to the synthetic procedure described in Example 25, 2-cyclopropyl-ethanol in place of 2-cyclopropyl-ethyl amine rac - {4 - [(3S , 4R) -3- (3,4- dichloro-phenyl ) -4-methylamino-pyrrolidine-1-carbonyl] -piperidin-1-yl} - (l-methanone in place of rac--cyclopropyl) {4 - [(3S, 4R) Yl} - (1-methyl-cyclopropyl) -methanone was prepared from 3- (4-chloro-phenyl) -4-methylamino- pyrrolidine- 1-carbonyll- piperidin- The title compound was prepared in analogy to the procedure described for the synthesis of rac-1 - {(3R, 4S) -4- (4-chloro-phenyl) Yl} -3- (2-cyclopropyl-ethyl) -l-methyl-urea as an off-white foam. MS m / e: 515.4 [M] ^&lt; ⁺ & gt ^; .

Example  59

 [(3R, 4S) -4- (3,4- Dichloro - Phenyl )-One-( Cis - 4- Hydroxy - Cyclohexanecarbonyl ) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

And

Example  60

[(3S, 4R) -4- (3,4- Dichloro - Phenyl )-One-( Cis - 4- Hydroxy - Cyclohexanecarbonyl ) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

rac - [(3R, 4S) -4- (3,4- dichloro-phenyl) -1- (cis-4-hydroxy-yl cyclohexane-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic Fluoro-phenyl ester was treated by column chromatography on a chiral tops to give [(3R, 4S) -4- (3,4-dichloro-phenyl) -l- ( cis - 4-hydroxy-cyclohexane carbon Methyl) -carbamic acid 4-fluoro-phenyl ester (MS (m / e): 509.3 [M] ⁺ ) - (3,4-dichloro-phenyl) -1- (cis-4-hydroxy-cyclohexane-carbonyl) -pyrrolidin-3-yl] - carbamic acid with 4-fluoro-phenyl-methyl ester (MS (m / e): 509.3 [M] ^&lt; ⁺ & gt ^; ) as an off-white foam.

Example  61

{(3R, 4R) -4- (3,4- Dichloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

And

Example  62

{(3S, 4S) -4- (3,4- Dichloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

rac - {(3R, 4R) -4- (3,4-Dichloro-phenyl) (3R, 4R) -4- (3,4-Dichloro-phenyl) -l- [l- (MS (m / e)), was prepared in accordance with the general method of example 1 from l- (l-methyl-cyclopropanecarbonyl) -piperidine-4-carbonyl] -pyrrolidin- : 576.2 [M] <^+> ) as a light brown oil and {(3S, 4S) -4- (3,4-dichloro- phenyl) Methyl-carbamic acid 4-fluoro-phenyl ester (MS (m / e): 576.2 [M] <^+> ) as a light brown oil.

Example  63

rac - {(3R, 4S) -4- (4- Chloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  2- Cyclopropyl - ethyl ester

And

Example  64

rac - {(3R, 4S) -4- (4- Chloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  2- Cyclopropyl - ethyl ester

rac - {(3R, 4S) -4- (4-Chloro-phenyl) -l- -Yl} -methyl-carbamic acid 2-cyclopropyl-ethyl ester was subjected to column chromatography on chiral top to give {(3R, 4S) -4- (4-chloro-phenyl) Methyl) -carbamic acid 2-cyclopropyl-ethyl ester (MS (m / e): 516.3 [M] ^&lt; ⁺ & gt ^; ) As an off-white foam and {(3S, 4R) -4- (4-chloro-phenyl) -l- 3-yl} -methyl-carbamic acid 2-cyclopropyl-ethyl ester (MS (m / e): 516.3 [M] <^+> ) as an off-white foam.

Example  65

rac - [(3R, 4S) -1- (1- Acetyl-piperidine-4-carbonyl) -4- (3,4-dichloro-phenyl) -pyrrolidin-3-yl] -methyl- Carbamic acid 4- fluoro - phenyl ester

In analogy to the synthetic procedure described in example 44 (step c), rac - [(3R, 4S) -4- (4-methylpiperidin-4- [(3R, 4S) -1- (l-acetyl-phenyl) -pyrrolidin-3- yl] -methyl- 4-carbonyl) -4- (3,4-dichloro-phenyl) -pyrrolidin-3-yl] -methyl- carbamic acid 4-fluoro-phenyl ester as a brown oil. MS m / e: 536.1 [M] ^&lt; ⁺ & gt ^; .

Example  66

rac -4 - {(3S, 4R) -3- (3,4- Dichloro - Phenyl ) -4 - [(4- Fluoro - Phenoxycarbonyl ) - methyl -Amino] - Pyrrolidine Carbonyl} -piperidin-l- Carboxylic acid  Tert-butyl ester

The title compound was synthesized in analogy to the synthetic procedure described in example 44 (step c) using rac - [((R) -methylpyrrolidin-1-yl) 4 - {(3S, 4R) -4-chloro-phenyl] -pyrrolidin- ) - 3- (3,4-dichloro-phenyl) -4 - [(4-fluoro-phenoxycarbonyl) -methyl- amino] -pyrrolidine- 1- carbonyl} -piperidin- -Carboxylic acid tert-butyl ester as a yellow foam. MS m / e: 593.1 [M] ^&lt; ⁺ & gt ^; .

Example  67

rac - {(3R, 4S) -4- (3,4- dichloro-phenyl) -1- [1- (1-cyclopenten one propane-carbonyl) -piperidine-4-carbonyl] -pyrrolidin Pyridin- 3 - yl} -methyl - carbamic acid 4,4,4 -trifluoro -butyl ester

Using 4,4,4-trifluorobutanol instead of 2-cyclopropylethanol in analogy to the synthetic procedure described in example 25, rac- {4 - [(3S, 4R) -3- (3,4- The title compound, rac - {(3R, 5S ) -7-methoxy-phenyll-4-methylamino-pyrrolidine- 4-carbonyl] -pyrrolidin-3-yl} - lH-pyrrolo [2,3-c] -Methyl-carbamic acid 4,4,4-trifluoro-butyl ester as an off-white foam. MS m / e: 592.3 [M] ^&lt; ⁺ & gt ^; .

Example  68

{(3R, 4S) -4- (3,4- Dichloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  (LR, 2S, 4S) - Bicyclo [2.2.1] hept Yl ester and {(3S, 4R) -4- (3,4- Dichloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  (LR, 2S, 4S) - Bicyclo [2.2.1] hept Yl ester

4- (3S, 4R) -3- (3,4-Dichloro-phenyl) - lH-pyrrolo [2,3-d ] pyrimidin- (3R, 4S) -4- (3-tert-butoxycarbonylamino-ethyl) -piperidine-l- -Pyrrolidin-3-yl} -methyl-carbamic acid (1R (2R, 3R) (2S, 4S) -bicyclo [2.2.1] hept-2-yl ester and {(3S, 4R) -4- Yl) -methyl-carbamic acid (lR, 2S, 4S) -bicyclo [2.2.1] hept-2-yl ester As an off-white foam. MS m / e: 576.3 [M] ^&lt; ⁺ & gt ^; .

Example  69

{(3R, 4S) -4- (3,4- Dichloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  (LR, 2R, 4S) - Bicyclo [2.2.1] hept Yl ester and {(3S, 4R) -4- (3,4- Dichloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  (LR, 2R, 4S) - Bicyclo [2.2.1] hept Yl ester

(3S, 4R) -3- (3,4-Dichloro-phenyl) - lH-pyrrolo [2,3-d ] pyrimidin- (3R, 4S) -4- (3-tert-butoxycarbonylamino-ethyl) -piperidine-l- -Pyrrolidin-3-yl} -methyl-carbamic acid (1R (2R, 3R) (2S, 4S) -bicyclo [2.2.1] hept-2-yl ester and {(3S, 4R) -4- Yl) -methyl-carbamic acid (lR, 2R, 4S) -bicyclo [2.2.1] hept-2-yl ester As an off-white foam. MS m / e: 576.3 [M] ^&lt; ⁺ & gt ^; .

Example  70

rac - {(3R, 4S) -4- (3- Chloro -4- methyl - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

a) rac- (3S, 4R) -l-Benzyl-3- (3 -chloro- 4- methyl - phenyl ) -4-nitro- pyrrolidine

Was prepared in analogy to the synthetic procedure described in example 1 (step a), but substituting 2-chloro-1-methyl-4- ((E) -2-nitro- (E) -2- nitro-vinyl) benzene the title compound, rac - (3S, 4R) -1- benzyl-3- (3-chloro-4-methyl-phenyl) -4-nitro-pyrrolidine light green As an oil. MS m / e: 331.1 [M] ^&lt; ⁺ & gt ^; .

b) rac - (3R, 4S ) -1- benzyl-4- (3-chloro-4-methyl-phenyl) -pyrrolidin-3-ylamine

In analogy with the synthesis procedure described in Example 1 (step b), rac - (3R, 4S) -1- benzyl-3- (3,4-dichloro-phenyl) -4-nitro-blood instead of pyrrolidine rac - (3S, 4R) -1- benzyl-3- (3-chloro-4-methyl-phenyl) -4-nitro-title compound was prepared from pyrrolidin-rac - (3R, 4S) -1- benzyl-4- ( 3-chloro-4-methyl-phenyl) -pyrrolidin-3-ylamine as a light brown oil. MS m / e: 301.2 [M + H] &lt; ⁺ &gt;.

c) rac - [(3R, 4S) -1- benzyl-4- (3-chloro-4-methyl-phenyl) -pyrrolidin-3-yl] -methyl-amine

(3S, 4R) -l-Benzyl-4- (3,4-dichloro-phenyl) -pyrrolidin-3-ylamine instead of rac- The title compound, rac - [(3R, 4S) -l-benzyl-piperazin-1- 4- (3-Chloro-4-methyl-phenyl) -pyrrolidin-3-yl] -methyl- amine as colorless oil. MS m / e: 315.1 [M + H] &lt; ⁺ &gt;.

d) rac - [(3R, 4S) -1- benzyl-4- (3-chloro-4-methyl-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid tert-butyl ester

In analogy to the synthetic procedure described in example 1 (step d), rac - [(3R, 4S) -l-benzyl- 4- (3,4- dichloro- phenyl) -pyrrolidin- methyl-amine in place of rac - [(3R, 4S) -1- benzyl-4- (3-chloro-4-methyl-phenyl) -pyrrolidin-3-yl] -methyl-amine the title compound, rac - [ (3R, 4S) -l-Benzyl-4- (3-chloro-4-methyl-phenyl) -pyrrolidin-3- yl] -methyl- carbamic acid tert- butyl ester as a light yellow oil. MS m / e: 415.3 [M + H] &lt; ⁺ &gt;.

e) rac - [(3R, 4S) -4- (3- chloro-4-methyl-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid tert-butyl ester

In analogy with the synthesis procedure described in Example 1 (step e), rac - [(3R , 4S) -1- benzyl-4- (3,4-dichloro-phenyl) -pyrrolidin-3-yl] - methyl-carbamic acid tert-butyl ester in place of rac - [(3R, 4S) -1- benzyl-4- (3-chloro-4-methyl-phenyl) -pyrrolidin-3-yl] -methyl-carbamic Butyl ester was prepared the title compound, rac - [(3R, 4S) -4- (3-chloro-4-methyl-phenyl) -pyrrolidin- Lt; / RTI &gt; as a brown foam. MS m / e: 271.3 [M + -tBu + H] &lt; ⁺ &gt;.

f) rac - {(3R, 4S) -4- (3- chloro-4-methyl-phenyl) -1- [1- (1-cyclopenten one propane-carbonyl) -piperidine-4-carbonyl] -pyrrolidin-3-yl} -methyl-carbamic acid tert-butyl ester

In analogy to the synthetic procedure described in example 1 (step f), rac - [(3R, 4S) -4- (3,4-dichloro- phenyl) -pyrrolidin- Butyl ester was prepared from rac - [(3R, 4S) -4- (3-chloro-4-methyl-phenyl) -pyrrolidin- compound rac - {(3R, 4S) -4- (3- chloro-4-methyl-phenyl) -1- [1- (1-methyl-cyclopropane-carbonyl) -piperidine-4-carbonyl] - Pyrrolidin-3-yl} -methyl-carbamic acid tert-butyl ester as a yellow oil. MS m / e: 518.3 [M] ^&lt; ⁺ & gt ^; .

g) rac - {4 - [ (3S, 4R) -3- (3- chloro-4-methyl-phenyl) -4-methylamino-pyrrolidine-1-carbonyl] -piperidin-1-yl } - (1- methyl - cyclopropyl ) -methanone

In analogy to the synthetic procedure described in example 2 (step a), rac - {(3R, 4S) -4- (3,4-dichloro- phenyl) yl) -piperidine-4-carbonyl] -pyrrolidin-3-yl} -methyl-carbamic acid tert-butyl ester in place of rac - {(3R, 4S) -4- (3- chloro-4 -Methyl-carbamic acid tert-butyl ester was prepared the title compound from the title compound as a white solid, MS (ISP) m / e calcd for &lt; RTI ID = compound rac - {4 - [(3S , 4R) -3- (3- chloro-4-methyl-phenyl) -4-methylamino-pyrrolidin-1-yl-carbonyl] - piperidin-1-yl} - (1-methyl-cyclopropyl) -methanone as a light brown oil. MS m / e: 418.4 [M + H] &lt; ⁺ &gt;.

h) rac - {(3R, 4S) -4- (3- chloro-4-methyl-phenyl) -1- [1- (1-cyclopenten one propane-carbonyl) -piperidine-4-carbonyl] -pyrrolidin-3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester

In analogy to the synthetic procedure described in example 2 (step b), rac - {4 - [(3S, 4R) -3- (3,4-Dichloro- phenyl) -4- methylamino-pyrrolidin- - carbonyl] -piperidin-1-yl} - (l-methyl-cyclopropyl) -methanone in place of rac - {4 - [(3S , 4R) -3- (3- chloro-4-methyl- phenyl) -4-methylamino-pyrrolidine-1-carbonyl] -piperidin-1-yl} - (l-methyl-cyclopropyl) - methanone The title compound from rac - {(3R, 4S) - 4-carbonyl] -pyrrolidin-3-yl} -methyl- cyclopropanecarbonyl) -piperidine-4- -Carbamic acid 4-fluoro-phenyl ester as an off-white foam. MS m / e: 566.2 [M] ^&lt; ⁺ & gt ^; .

Example  71

rac - {(3R, 4S) -4- (4- Chloro -3- methyl - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

a) rac- (3S, 4R) -l-Benzyl-3- (4 -chloro- 3- methyl - phenyl ) -4-nitro- pyrrolidine

Was prepared in analogy to the synthetic procedure described in example 1 (step a) from l-chloro-2-methyl-4- ((E) (E) -2- nitro-vinyl) benzene the title compound, rac - (3S, 4R) -1- benzyl-3- (4-chloro-3-methyl-phenyl) -4-nitro-pyrrolidine light green As an oil. MS m / e: 331.1 [M] ^&lt; ⁺ & gt ^; .

b) rac - (3R, 4S ) -1- benzyl-4- (4-chloro-3-methyl-phenyl) -pyrrolidin-3-ylamine

In analogy with the synthesis procedure described in Example 1 (step b), rac - (3R, 4S) -1- benzyl-3- (3,4-dichloro-phenyl) -4-nitro-blood instead of pyrrolidine rac - (3S, 4R) -1- benzyl-3- (4-chloro-3-methyl-phenyl) -4-nitro-title compound was prepared from pyrrolidin-rac - (3R, 4S) -1- benzyl-4- ( Chloro-3-methyl-phenyl) -pyrrolidin-3-ylamine as a dark brown oil. MS m / e: 301.2 [M + H] &lt; ⁺ &gt;.

c) rac - [(3R, 4S) -1- benzyl-4- (4-chloro-3-methyl-phenyl) -pyrrolidin-3-yl] -methyl-amine

(3S, 4R) -l-Benzyl-4- (3,4-dichloro-phenyl) -pyrrolidin-3-ylamine instead of rac- The title compound, rac - [(3R, 4S) -l-benzyl-piperazin-1- Chloro-3-methyl-phenyl) -pyrrolidin-3-yl] -methyl-amine as a pale yellow oil. MS m / e: 315.1 [M + H] &lt; ⁺ &gt;.

d) rac - [(3R, 4S) -1- benzyl-4- (4-chloro-3-methyl-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid tert-butyl ester

In analogy to the synthetic procedure described in example 1 (step d), rac - [(3R, 4S) -l-benzyl- 4- (3,4- dichloro- phenyl) -pyrrolidin- methyl-amine in place of rac - [(3R, 4S) -1- benzyl-4- (4-chloro-3-methyl-phenyl) -pyrrolidin-3-yl] -methyl-amine the title compound, rac - [ 3-yl] -methyl-carbamic acid tert-butyl ester as a pale yellow oil. MS m / e: 415.3 [M + H] &lt; ⁺ &gt;.

e) rac - [(3R, 4S) -4- (4- chloro-3-methyl-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid tert-butyl ester

In analogy with the synthesis procedure described in Example 1 (step e), rac - [(3R , 4S) -1- benzyl-4- (3,4-dichloro-phenyl) -pyrrolidin-3-yl] - methyl-carbamic acid tert-butyl ester in place of rac - [(3R, 4S) -1- benzyl-4- (4-chloro-3-methyl-phenyl) -pyrrolidin-3-yl] -methyl-carbamic The title compound, rac - [(3R, 4S) -4- (4-chloro-3-methyl-phenyl) -pyrrolidin- 3- yl] -methyl-carbamic acid tert- butyl ester Lt; / RTI &gt; as a brown oil. MS m / e: 271.3 [M + -tBu + H] &lt; ⁺ &gt;.

f) rac - {(3R, 4S) -4- (4- chloro-3-methyl-phenyl) -1- [1- (1-cyclopenten one propane-carbonyl) -piperidine-4-carbonyl] -pyrrolidin-3-yl} -methyl-carbamic acid tert-butyl ester

In analogy to the synthetic procedure described in example 1 (step f), rac - [(3R, 4S) -4- (3,4-dichloro- phenyl) -pyrrolidin- Butyl ester was prepared from rac - [(3R, 4S) -4- (4-chloro-3-methyl-phenyl) -pyrrolidin- compound rac - {(3R, 4S) -4- (4- chloro-3-methyl-phenyl) -1- [1- (1-methyl-cyclopropane-carbonyl) -piperidine-4-carbonyl] - Pyrrolidin-3-yl} -methyl-carbamic acid tert-butyl ester as a yellow oil. MS m / e: 518.4 [M] ^&lt; ⁺ & gt ^; .

g) rac - {4 - [ (3S, 4R) -3- (4- chloro-3-methyl-phenyl) -4-methylamino-pyrrolidine-1-carbonyl] -piperidin-1-yl } - (1- methyl - cyclopropyl ) -methanone

In analogy to the synthetic procedure described in example 2 (step a), rac - {(3R, 4S) -4- (3,4-dichloro- phenyl) (3R, 4S) -4- (4-chloro-3-methyl-butyramide instead of rac -3-yl-piperidin- -Methyl-carbamic acid tert-butyl ester was prepared the title compound from the title compound as a white solid, MS (ISP) m / e calcd for &lt; RTI ID = compound rac - {4 - [(3S , 4R) -3- (4- chloro-3-methyl-phenyl) -4-methylamino-pyrrolidin-1-yl-carbonyl] - piperidin-1-yl} - (1-methyl-cyclopropyl) -methanone as a pale yellow oil. MS m / e: 418.2 [M + H] &lt; ⁺ &gt;.

h) rac - {(3R, 4S) -4- (4- chloro-3-methyl-phenyl) -1- [1- (1-cyclopenten one propane-carbonyl) -piperidine-4-carbonyl] -pyrrolidin-3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester

In analogy to the synthetic procedure described in example 2 (step b), rac - {4 - [(3S, 4R) -3- (3,4-Dichloro- phenyl) -4- methylamino-pyrrolidin- - carbonyl] -piperidin-1-yl} - (l-methyl-cyclopropyl) -methanone in place of rac - {4 - [(3S , 4R) -3- (4- chloro-3-methyl- phenyl) -4-methylamino-pyrrolidine-1-carbonyl] -piperidin-1-yl} - (l-methyl-cyclopropyl) - methanone The title compound from rac - {(3R, 4S) - 4-carbonyl] -pyrrolidin-3-yl} -methyl- cyclopentanecarbonyl) -piperidine-4- -Carbamic acid 4-fluoro-phenyl ester as an off-white foam. MS m / e: 566.2 [M] ^&lt; ⁺ & gt ^; .

Example  72

rac - [(3R, 4S) -4- (3,4- dichloro-phenyl) -1- (piperidin-4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4- Fluoro - phenyl ester

In analogy to the synthetic procedure described in example 2 (step a), rac - {(3R, 4S) -4- (3,4-dichloro- phenyl) 4 - {(3S, 4R) -3- (3,4-dihydro-pyrazol-4-ylmethyl) -piperidine- Carboxylic acid tert-butyl ester as a light yellow solid. MS: m / e = 366.1 (M + H) The title compound was prepared in analogy to the procedure described for the synthesis of rac - [(3R, 4S) -4- (3,4-dichloro-phenyl) -l- (piperidine- 4- carboyl) -pyrrolidin- 4-fluoro-phenyl ester as a pale yellow foam. MS m / e: 494.2 [M] ^&lt; ⁺ & gt ^; .

Example  73

rac - [(3R, 4S) -4- (3,4- dichloro-phenyl) -1- (1-propionyl-piperidine-4-carbonyl) -pyrrolidin-3-yl] -methyl -carbamic acid 4-fluoro-phenyl ester

To a solution of rac - [(3R, 4S) -4- (3,4-dichloro-phenyl) -l- (piperidine- 4- 4- carbonyl) -pyrrolidin- N, N-diisopropylethylamine (208 [mu] l, 1.21 mmol) was added to a solution of methyl-carbamic acid 4-fluoro-phenyl ester (200 mg, 0.41 mmol). After stirring for 5 min, propionyl chloride (53 [mu] L, 0.61 mmol) was added. After stirring at ambient temperature for 3 hours, the reaction mixture was treated with an aqueous solution of sodium carbonate (1 M, 10 mL). The organic layer was separated, washed with brine (10 mL) and the aqueous layer was extracted with ethyl acetate (20 mL). The combined organic layers were dried over sodium sulfate and concentrated. Chromatography (SiO _2, ethyl acetate: methanol = 100: 0 to 80:20) to obtain the title compound (88 mg, 40%) was obtained as a white solid. MS m / e: 550.3 [M] ^&lt; ⁺ & gt ^; .

Example  74

rac - [(3R, 4S) -1- (1-cyclopropanecarbonyl-piperidine-4-carbonyl) -4- Dichloro - Phenyl ) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

In analogy to the synthetic procedure described in example 73, rac - [(3R, 4S) -4- (3,4-dichloro-phenyl) -l- (piperidine- 4- carbonyl) -pyrrolidine- 3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester using cyclopropanecarbonyl chloride instead of propionyl chloride the title compound rac - [(3R, 4S) -1- (1-cyclopropanecarbonyl -Piperidin-4-carbonyl) -4- (3,4-dichloro-phenyl) -pyrrolidin-3-yl] -methyl- carbamic acid 4-fluoro-phenyl ester as a white foam . MS m / e: 562.1 [M] ^&lt; ⁺ & gt ^; .

Example  75

rac - {(3R, 4S) -4- (3,4- dichloro-phenyl) -1- [1- (2-methoxy-acetyl) -piperidine-4-carbonyl] -pyrrolidin- 3-yl} -methyl - carbamic acid 4- fluoro - phenyl ester

In analogy to the synthetic procedure described in example 73, rac - [(3R, 4S) -4- (3,4-dichloro-phenyl) -l- (piperidine- 4- carbonyl) -pyrrolidine- 3-yl] -methyl-carbamic acid 4-fluoro-using methoxyacetyl chloride in place of propionyl chloride from phenyl ester the title compound, rac - {(3R, 4S) -4- (3,4- dichloro- 4-carbonyl] -pyrrolidin-3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester was obtained as a white foam . MS m / e: 566.3 [M] ^&lt; ⁺ & gt ^; .

Example  76

rac - {(3R, 4S) -4- (3,4- Dichloro - Phenyl ) -1- [1- ( Tetrahydro -Pyran-4-carbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

In analogy to the synthetic procedure described in example 73, rac - [(3R, 4S) -4- (3,4-dichloro-phenyl) -l- (piperidine- 4- carbonyl) -pyrrolidine- 3-yl] -methyl-carbamic acid 4-fluoro-use the pyran-4-carbonyl chloride the title compound, rac--tetrahydro -2 H in place of propionyl chloride from phenyl ester {(3R, 4S) -4 - (3,4-dichloro-phenyl) -l- [l- (tetrahydro-pyran-4-carbonyl) -piperidine-4- carbonyl] -pyrrolidin- Carbamic acid 4-fluoro-phenyl ester as a white foam. MS m / e: 606.3 [M] ^&lt; ⁺ & gt ^; .

Example  77

rac - {(3R, 4S) -4- (3,4- Dichloro - Phenyl ) -1- [1- ( Tetrahydro -Pyran-4-yl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

Example 44 in place (Step c) In analogy to the synthesis procedure, 1-methyl-cyclopropane-1-carboxylic acid as described in 1- (tetrahydropyran-4-yl) - using -piperidine-4-carboxylic acid rac - [(3R, 4S) -4- (3,4-dichloro-phenyl) -l- (piperidine-4- carbonyl) -pyrrolidin- in-title compound was prepared from the phenyl ester rac - {(3R, 4S) -4- (3,4- dichloro-phenyl) -1- [1- (tetrahydropyran-4-yl) -piperidin-4 -Carbonyl] -pyrrolidin-3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester as an off-white foam. MS m / e: 578.2 [M] ^&lt; ⁺ & gt ^; .

Example  78

rac - [(3R, 4S) -4- (3,4- dichloro-phenyl) -1- (1- [1, 3,4] thiadiazine-2-yl-piperidine-4-carbonyl ) -Pyrrolidin- 3 - yl] -methyl - carbamic acid 4- fluoro - phenyl ester

To a solution of rac - [(3R, 4S) -4- (3,4-dichloro-phenyl) -l- (piperidine-4- carbonyl) -pyrrolidin- Bromo-l, 3,4-thiadiazole (50 mg, 0.30 mmol) and N, N-diisopropylethylamine were added to a solution of 2-bromo- N-diisopropylethylamine (69 [mu] L, 0.40 mmol) was added. The solution was irradiated with microwave at 150 &lt; 0 &gt; C for 35 minutes. The reaction mixture was diluted with ethyl acetate (15 mL) and washed with an aqueous solution of sodium carbonate (1 M, 15 mL). The organic layer was separated, washed with brine (15 mL) and the aqueous layer was extracted with ethyl acetate (20 mL). The combined organic layers were dried over sodium sulfate and concentrated. Chromatography (SiO _2, ethyl acetate: methanol = 100: 0 to 80:20) to obtain the title compound (37 mg, 32%) as an off-white foam in yield. MS m / e: 578.1 [M] ^&lt; ⁺ & gt ^; .

Example  79

rac - [(3R, 4S) -1- [1- (6- chloro-3-yl) -piperidine-4-carbonyl] -4- (3,4-dichloro-phenyl) - Pyrrolidin- 3 - yl] -methyl - carbamic acid 4- fluoro - phenyl ester

Example 44 In analogy to the synthetic procedures described in the (step c), 1-methyl-cyclopropane-1-carboxylic acid in place of using the 1- (6-chloro-3-pyridazinyl) -4-piperidine-carboxylic acid rac - [(3R, 4S) -4- (3,4- dichloro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-title compound was prepared from the phenyl ester rac - [(3R, 4-carbonyl] -4- (3,4-dichloro-phenyl) -pyrrolidine-3- Yl] -methyl-carbamic acid 4-fluoro-phenyl ester as an off-white foam. MS m / e: 608.1 [M + H] &lt; ⁺ &gt;.

Example  80

rac - [(3R, 4S) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] Bipyridinyl -4-carbonyl) -4- (3,4- Dichloro - Phenyl ) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- (piperidine-4-carbonyl) -pyrrolidin- 3- (50 mg, 0.10 mmol) and 6-chloronicotinonitrile (21 mg, 0.15 mmol) in N, N-diisopropylethylamine , 0.30 mmol). The solution was stirred at ambient temperature for 6 h, then diluted with ethyl acetate (15 mL) and washed with an aqueous solution of sodium carbonate (1 M, 15 mL). The organic layer was separated, washed with brine (15 mL) and the aqueous layer was extracted with ethyl acetate (20 mL). The combined organic layers were dried over sodium sulfate and concentrated. Chromatography (SiO _2, heptane: ethyl acetate: methanol = 80:: 20 0 to 0:90:10) afforded the title compound (52 mg, 86%) as an off-white foam in yield. MS m / e: 596.2 [M] ^&lt; ⁺ & gt ^; .

Example  81

{(3R, 4S) -4- (3,4- Dichloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4,4,4- Trifluro - butyl ester

And

Example  82

{(3S, 4R) -4- (3,4- Dichloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4,4,4- Trifluro - butyl ester

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- 3-yl} -methyl-carbamic acid 4,4,4-trifluoro-butyl ester was chromatographed on chiral top to give {(3R, 4S) -4- (3,4- ) - l- [l- (1 -methyl-cyclopropanecarbonyl) -piperidine-4-carbonyl] -pyrrolidin-3- yl} -methyl- carbamic acid 4,4,4- trifluoro -Butyl ester (MS (m / e): 592.3 [M] ⁺ ) as an off-white foam and {(3S, 4R) -4- (3,4- Methyl) -carbamic acid 4,4,4-trifluoro-butyl ester (MS (m / e) &lt; : 592.3 [M] ^&lt; ⁺ & gt ^; ) as an off-white foam.

Example  83

rac - {(3R, 4S) -4- (3,4- Dichloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  3,3,4,4,4- Pentafluoro - butyl ester

In analogy with the synthesis procedure described in example 25, rac - {4 - [ (3S, 4R) -3- (3,4- dichloro-phenyl) -4-methylamino-pyrrolidine-1-carbonyl] -Piperidine-l-yl} - (1-methyl-cyclopropyl) -methanone was prepared using 3,3,4,4,4,4-pentafluorobutan- l-ol instead of 2-cyclopropylethanol The title compound was prepared in analogy to the procedure described for the synthesis of rac - {(3R, 4S) -4- (3,4-dichloro-phenyl) Pyrrolidin-3-yl} -methyl-carbamic acid 3,3,4,4,4-pentafluoro-butyl ester as a white foam. MS m / e: 628.2 [M] ^&lt; ⁺ & gt ^; .

Example  84

rac - {(3R, 4S) -4- (3,4- Dichloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  (S) -1- ( Tetrahydro -Furan-2-yl) methyl  Esters and rac - {(3R, 4S) -4- (3,4- Dichloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  (R) -1- ( Tetrahydro -Furan-2-yl) methyl  Ester

In analogy with the synthesis procedure described in example 25, rac - {4 - [ (3S, 4R) -3- (3,4- dichloro-phenyl) -4-methylamino-pyrrolidine-1-carbonyl] -piperidin-1-yl} - (l-methyl-cyclopropyl) - 2-cyclopropyl-ethanol in place of using rac- tetrahydro-furan-3-methanol the title compound from -methanone rac - {(3R, 4S Yl) -piperidin-4-carbonyl] -pyrrolidin-3-yl} - (4- Methyl-carbamic acid (S) -l- (tetrahydro-furan-2-yl) methyl ester and rac - {(3R, 4S) -4- (3,4- (R) -l- (tetrahydro-furan-2-yl) -piperidine-4-carbonyl] -pyrrolidin- Methyl ester as an off-white foam. MS m / e: 566.2 [M] ^&lt; ⁺ & gt ^; .

Example  85

rac - {(3R, 4S) -4- (3,4- Dichloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  (S) -1- ( Tetrahydro -Furan-3-yl) methyl  Esters and rac - {(3R, 4S) -4- (3,4- Dichloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  (R) -1- ( Tetrahydro -Furan-3-yl) methyl  Ester

In analogy with the synthesis procedure described in example 25, rac - {4 - [ (3S, 4R) -3- (3,4- dichloro-phenyl) -4-methylamino-pyrrolidine-1-carbonyl] -piperidin-1-yl} - (l-methyl-cyclopropyl) - 2-cyclopropyl-ethanol in place of using the title compound from rac- tetrahydro furyl alcohol -methanone rac - {(3R, 4S) -4 - (3,4-dichloro-phenyl) -l- [l- (1 -methyl- cyclopropanecarbonyl) -piperidine-4- carbonyl] -pyrrolidin-3- yl} Yl) methyl ester and rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) Methyl-cyclopropanecarbonyl) -piperidine-4-carbonyl] -pyrrolidin-3-yl} -methyl- carbamic acid (R) -l- (tetrahydro- As a white foam. MS m / e: 566.2 [M] ^&lt; ⁺ & gt ^; .

Example  86

rac - {(3R, 4S) -4- (3,4- Dichloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  3,3,3- Trifluro -Profile ester

And

Example  87

rac - {(3R, 4S) -4- (3,4- Dichloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  3,3,3- Trifluro -Profile ester

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- 3-yl} -methyl-carbamic acid 3,3,3-trifluoro- propyl ester was chromatographed on chiral top to give {(3R, 4S) -4- (3,4- ) - l- [l- (1 -methyl-cyclopropanecarbonyl) -piperidine-4-carbonyl] -pyrrolidin-3- yl} -methyl- carbamic acid 3,3,3-trifluoro -Propyl ester (MS (m / e): 578.3 [M] ⁺ ) as an off-white foam and {(3S, 4R) -4- (3,4- Methyl) -carbamic acid 3,3,3-trifluoro-propyl ester (MS (m / e) &lt; : 578.3 [M] ^&lt; ⁺ & gt ^; ) as an off-white foam.

Example  88

rac - {(3R, 4S) -4- (3,4- dichloro-phenyl) -1- [1- (1-cyclopenten one propane-carbonyl) -piperidine-4-carbonyl] -pyrrolidin Pyridin - 3 - yl} -methyl - carbamic acid 4,4,5,5,5- pentafluoro - pentyl ester

In analogy with the synthesis procedure described in example 25, rac - {4 - [ (3S, 4R) -3- (3,4- dichloro-phenyl) -4-methylamino-pyrrolidine-1-carbonyl] -piperidin-1-yl} - (l-methyl-cyclopropyl) - using a 4,4,5,5,5- pentafluoro-pentanol in place of 2-cyclopropyl ethanol from -methanone the title compound, rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- Yl} -methyl-carbamic acid 4,4,5,5,5-pentafluoro-pentyl ester as an off-white foam. MS m / e: 642.2 [M] ^&lt; ⁺ & gt ^; .

Example  89

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (4- Hydroxy - Cyclohexanecarbonyl ) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

a) ( 4 -Chloro - phenyl ) -propionic acid ethyl ester

A mixture of 1-chloro-4-iodobenzene (120.4 g, 0.50 mol) and cesium carbonate (352.8 g, 1.0 mol) in tetrahydrofuran (1.275 L) was purged and flushed with argon. Ethyl propiolate (100 g, 1.01 mol) was added to a solution of 20 (20.0 mmol) of bis (triphenylphosphine) palladium (II) chloride (7.02 g, 10.0 mmol) Min. &Lt; / RTI &gt; After the dark brown suspension produced was stirred at 35 ℃ for 41 hours and filtered over hyflo (Hyflo ^®), and washed with THF (5 L). The solution was concentrated, treated with 1: 2 toluene / heptane (1.5 L) and stirred at 45 C for 1 h under reduced pressure (250 mbar). The resulting suspension was filtered and the residue was washed with additional 1: 2 toluene / heptane (1.5 L). The solid was dried to give a dark brown oil of 181.64 g (MS m / e: 209.0 / 211.2 [M + H] ⁺ ) as a crude product which was used without further purification.

b) 1- Benzyl-4- (4-chloro-phenyl) -2,5-dihydro -1H- pyrrole-3-carboxylic acid

Trifluoroacetic acid (3.4, 44.4 mmol) was added to a solution of (4-chloro-phenyl) -propionic acid ethyl ester (92.65 g, 444.1 mmol) in dichloromethane (425 mL). The reaction mixture was cooled in a water bath and a solution of N- (methoxymethyl) -N- (trimethylsilylmethyl) benzylamine (164.7 g, 666.1 mmol) in dichloromethane (325 mL) was added dropwise over 1.5 hours . It was stirred at ambient temperature for 22 hours. Additional N- (methoxymethyl) -N- (trimethylsilylmethyl) benzylamine (27.5 g, 111.0 mmol) in dichloromethane (50 mL) was added and stirring continued for 2 h at ambient temperature. The solvent was distilled off and the residue was taken up in dioxane (950 mL). Water (475 mL) and sodium hydroxide (32%, 114.3 mL, 1.23 mol) were added and stirred at ambient temperature for 67 hours. After concentration, the residue was diluted with water (400 mL) and extracted with tert-butyl methyl ether (400 mL). The organic layer was washed with water (400 mL). The aqueous layers were combined, cooled to 5 &lt; 0 &gt; C and the pH was adjusted to 1.5 using aqueous HCl (25%, 172). After stirring at 5 &lt; 0 &gt; C for 1 hour, the solid was filtered and washed with water (1400 mL) and ethanol (400 mL). Dried (50 DEG C, 25 mbar) to give the title compound (109.85 g, 79%) as an off-white solid. MS m / e: 312.2 / 314.1 [MH] ^&lt;&quot;&gt;.

c) (3R, 4R) -1- benzyl-4- (4-chloro-phenyl) -pyrrolidine-3-carboxylic acid

Glove box, a 1-benzyl autoclave under argon (O ₂ content <2 ppm) -4- (4- chloro-phenyl) -2,5-dihydro -1H- pyrrole-3-carboxylic acid (1.00 g, 3.19 mmol ), [Ru (OAc) ₂ ( S ) -2-furyl-MeOBIPHEP)] (9.72 mg, 0.01 mmol) (2-furyl-MeOBIPHEP = (6,6'-dimethoxybiphenyl- 2-furylphosphine) and methanol (30 ml) at 30 ° C under a hydrogen atmosphere (> 95% conversion, measured by NMR) at 40 bar (bar) The crude product was dissolved in methanol (15 mL) and heated to reflux for 1 hour. After cooling to ambient temperature, the crude product was purified by flash chromatography (0.984 g, 95%, ee 99.8% R, R (chiral HPLC)) was added dropwise to the resulting suspension, which was filtered and dried for 2 hours Obtained as a white solid MS m / e: 316.1 [M + H] ⁺ .

d) (3R, 4R) -1- benzyl-4- (4-chloro-phenyl) -pyrrolidine-3-carboxylic acid Methyl ester

To a white suspension of (3R, 4R) -l-benzyl-4- (4-chloro-phenyl) -pyrrolidine-3-carboxylic acid (72.31 g, 229 mmol) in methanol (725 mL) mmol) was added slowly. The resulting dark brown solution was stirred at 60 &lt; 0 &gt; C for 19 hours. After cooling to 0 C, tert-butyl methyl ether (1.6 L) was added and the solution was adjusted to pH 9 using aqueous sodium carbonate (IM, 480 mL). The aqueous layer was separated and further extracted with tert-butyl methyl ether (410 mL). The organic layer was washed with brine (310 mL) and dried over sodium sulfate. Concentration gave the title compound (74.18 g, 98%) as a light brown oil. MS m / e: 330.3 / 332.3 [M + H] &lt; ⁺ &gt;.

e) (3S, 4R) -1- benzyl-4- (4-chloro-phenyl) -pyrrolidine-3-carboxylic acid Methyl ester

To a solution of (3R, 4R) -l-benzyl-4- (4-chloro-phenyl) -pyrrolidine-3-carboxylic acid methyl ester (72.74 g, 220.5 mmol) in methanol (730 mL) 5.4 M methanol, 81.7 mL, 441.1 mmol). The reaction mixture was stirred at ambient temperature (17.5 hours later addition of sodium methylate solution (5.4M in methanol, 20.4 mL, 110.3 mmol)) for 116 hours. The pH was adjusted to 1 by addition of sulfuric acid (26.13 mL, 463.1 mmol) and stirred at 60 &lt; 0 &gt; C for 19 hours. The resulting suspension was cooled to 0 C, tert-butyl methyl ether (1.6 L) was added and the solution was adjusted to pH 9 using aqueous sodium carbonate (IM, 440 mL). The aqueous layer was separated and extracted with additional tert-butyl methyl ether (410 mL). The organic layer was washed with brine (310 mL), combined and dried over sodium sulfate. Concentration and filtration over silica gel (heptane: ethyl acetate = 80:20) afforded the title compound (62.82 g, 86%) as a pale yellow oil. MS m / e: 330.3 / 332.3 [M + H] &lt; ⁺ &gt;.

f) (3S, 4R) -1- benzyl-4- (4-chloro-phenyl) -pyrrolidine-3-carboxylic acid Amide

(62.82 g, 190.5 mmol) and formamide (22.7 mL, 571.4 mmol) in DMF (75 mL) was added dropwise to a solution of (3S, 4R) mmol) was heated to 100 &lt; 0 &gt; C. A solution of sodium methylate (5.4 M in methanol, 17.6 mL, 95.2 mmol) was then added dropwise over 50 minutes. The solution was stirred at 100 &lt; 0 &gt; C (1 hour later, additional formamide (11.4 mL, 285.7 mmol) was added) for 3 hours. The reaction mixture was cooled to ambient temperature and the resulting suspension was partitioned between ethyl acetate (1500 mL) and water (1000 mL). The organic layer was washed with brine (500 mL), combined and dried over sodium sulfate. Concentration and trituration with tert-butyl methyl ether (500 mL) gave the title compound (51.19 g, 85%) as white crystals. MS m / e: 315.2 and 317.3 [M + H] &lt; ⁺ &gt;).

g) [(3S, 4R) -1- benzyl-4- (4-chloro-phenyl) -pyrrolidin-3-yl] -carbamic acid Methyl ester

To a solution of potassium hydroxide (25.09 g, 447.2 mmol) in methanol (520 mL) was added (3S, 4R) -l-benzyl- 4- (4- chloro- phenyl) -pyrrolidine- 3-carboxylic acid amide (51.19 g, 162.6 mmol). After cooling to 0 &lt; 0 &gt; C, diethoxy iodosobenzene (57.61 g, 178.9 mmol) was added. The reaction mixture was stirred at 0 &lt; 0 &gt; C for 45 minutes and 1.5 hours at ambient temperature and then diluted with water (1000 mL). The mixture was separated between dichloromethane (1500 mL) and aqueous sodium carbonate (IM, 1000 mL). The organic layer was washed with brine (750 mL), combined, and dried over sodium sulfate. Concentration and trituration with tert-butyl methyl ether (180 mL) gave the title compound (49.22 g, 88%) as a white solid. MS m / e: 345.3 and 347.2 [M + H] &lt; ⁺ &gt;).

h) [(3S, 4R) -1- benzyl-4- (4-chloro-phenyl) -pyrrolidin-3-yl] -methyl-amine

To a suspension of [(3S, 4R) -1-benzyl-4- (4-chloro-phenyl) -pyrrolidin-3- yl] -carbamic acid methyl ester (49.22 g, 142.7 mmol) in THF (520 mL) A solution of borane-tetrahydrofuran complex (1M in tetrahydrofuran, 571 mL, 571 mmol) was slowly added over 25 minutes. The reaction mixture was stirred at 60 &lt; 0 &gt; C for 19 h and then quenched with aqueous HCl (IN, 570 mL, added dropwise over 60 min). The mixture was further stirred at 60 &lt; 0 &gt; C for 21 h. After cooling to ambient temperature, the tetrahydrofuran was distilled off and the residue was partitioned between tert-butyl methyl ether (1500 mL) and aqueous HCl (1 N, 1000 mL). The aqueous layer was adjusted to pH 10 using aqueous sodium carbonate (sat., 2000 mL) and then extracted with tert-butyl methyl ether (1500 mL twice). The organic layer was washed with brine (750 mL), combined, and dried over sodium sulfate. Concentration and filtration over silica gel (ethyl acetate: methanol, triethylamine = 90: 5: 5) gave the title compound (34.38, 80%) as a pale yellow liquid. MS m / e: 301.4 / 303.4 [M + H] &lt; ⁺ &gt;.

i) [(3S, 4R) -l-Benzyl-4- (4 -chloro - phenyl ) -pyrrolidin- 3- yl] -methyl - carbamic acid 4- fluoro - phenyl ester

(3S, 4R) -3- (3,4-Dichloro-phenyl) -4, 4-dihydro- 2H - isoquinolin -2-one using analogous procedure to that described in example 2 (3S, 4R) -l-benzyl-4- ((2-methyl-pyridin-l-yl) -piperidin- (4-chloro-phenyl) -pyrrolidin-3-yl] -methyl- amine was prepared the title compound [(3S, 4R) ] -Methyl-carbamic acid 4-fluoro-phenyl ester as a light brown oil. MS m / e: 439.2 [M + H] &lt; ⁺ &gt;.

j) [(3S, 4R) -4- (4- chloro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester

In analogy with the synthesis procedure described in Example 1 (step e), rac - [(3R , 4S) -1- benzyl-4- (3,4-dichloro-phenyl) -pyrrolidin-3-yl] - (4-chloro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid tert-butyl ester was prepared in analogy to the procedure described for the synthesis of [(3S, 4R) 4-chloro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester as a light brown oil. MS m / e: 349.2 [M + H] &lt; ⁺ &gt;.

k) [(3S, 4R) -4- (4-chloro-phenyl) -1- (4-hydroxy-cyclohexane-carbonyl) -pyrrolidin-3-yl] - carbamic acid with 4-fluoro-methyl - phenyl ester

The title compound was prepared in analogy to the synthetic procedure described in example 44 (step c), using trans-4-hydroxycyclohexanecarboxylic acid instead of 1-methylcyclopropane-l-carboxylic acid to give rac - [(3S, 4R) -4- (3S, 4R) -4- (4-chloro-phenyl) -piperidine instead of 4-chloro-phenyl) -pyrrolidin- (4-chloro-phenyl) -l- (4-hydroxy-cyclohexanecarboxine &lt; / RTI &gt; Yl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester as an off-white foam. MS m / e: 475.2 [M + H] &lt; ⁺ &gt;.

Example  90

[(3S, 4R) -4- (4- Chloro - Phenyl )-One-( Tetrahydro -Pyran-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

The title compound was prepared in analogy to the synthetic procedure described in example 44 (step c) using rac - [(3S, 4R) -4- ( (3S, 4R) -4- (4-chloro-phenyl) -piperidine instead of 4-chloro-phenyl) -pyrrolidin- (4-chloro-phenyl) -l- (tetrahydro-pyran-4-carbonyl) Yl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester as an off-white foam. MS m / e: 461.2 [M + H] &lt; ⁺ &gt;.

Example  91

rac - {(3R, 4S) -4- (3,4- Dichloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  One- methyl - Cyclopropylmethyl  Ester

In analogy to the synthetic procedure described in example 25, by using 1-methylcyclopropane methanol instead of 2-cyclopropylethanol, rac - {4 - [(3S, 4R) -3- (3,4- ) -4-methylamino-pyrrolidine-1-carbonyl] -piperidin-1-yl} - (l-methyl-cyclopropyl) - methanone The title compound from rac - {(3R, 4S) -4 - (3,4-dichloro-phenyl) -l- [l- (1 -methyl- cyclopropanecarbonyl) -piperidine-4- carbonyl] -pyrrolidin-3- yl} Methyl-cyclopropylmethyl ester as an off-white foam. MS m / e: 550.2 [M] &lt; ⁺ & gt ^; .

Example  92

rac - {(3R, 4S) -4- (3,4- dichloro-phenyl) -1- [1- (1-cyclopenten one propane-carbonyl) -piperidine-4-carbonyl] -pyrrolidin Pyridin- 3 - yl} -methyl - carbamic acid 2- methyl - cyclopropylmethyl ester

Example In analogy to the procedure described in Synthesis 25, using 2-cyclopropyl-2-methyl-cyclopropane methanol in place of ethanol (mixture of cis / trans) rac - {4 - [( 3S, 4R) -3- (3 -Acetic acid was prepared from rac - {(4-chloro-phenyl) -4-methylamino-pyrrolidine- 1-carbonyl] -piperidin- (3R, 4S) -4- (3,4-Dichloro-phenyl) -l- -Yl} -methyl-carbamic acid 2-methyl-cyclopropylmethyl ester as an off-white foam. MS m / e: 550.2 [M] &lt; ⁺ & gt ^; .

Example  93

 [(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (1,1- Dioxo - Hexahydro -1λ ⁶ - Thiopyran Carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

In analogy to the synthetic procedure described in example 44 (step c), using l, l-dioxo-hexahydro-l [lambda] ⁶ -thiopyran-4-carboxylic acid instead of 1- methylcyclopropane- The title compound was prepared from the title compound [(3S, 4R) -4- (4-chloro-phenyl) -pyrrolidin- (L, l-dioxo-hexahydro-l [lambda] ⁶ -thiopyran-4-carbonyl) -pyrrolidin-3- yl] -methyl- carbamic acid 4- fluoro -Phenyl &lt; / RTI &gt; ester as an off-white foam. MS m / e: 509.1 [M] ^&lt; ⁺ & gt ^; .

Example  94

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] &lt; / RTI & Epithe 4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

The title compound was prepared in analogy to the synthetic procedure described in example 44 (step c) from 5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 ' ] Bipyridinyl-4-carboxylic acid was prepared from [(3S, 4R) -4- (4-chloro-phenyl) -pyrrolidin- [(3S, 4R) -4- (4-Chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro- 4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester as an off-white foam. MS m / e: 562.1 [M] ^&lt; ⁺ & gt ^; .

Example  95

rac - {(3R, 4S) -4- (3,4- dichloro-phenyl) -1- [1- (1-cyclopenten one propane-carbonyl) -piperidine-4-carbonyl] -pyrrolidin Pyridin- 3 - yl} -methyl - carbamic acid 4- fluoro -benzyl ester

In analogy to the synthetic procedure described in example 25, rac - {4- [(3S, 4R) -3- (3,4-dichloro-phenyl) -piperidine- ) -4-methylamino-pyrrolidine-1-carbonyl] -piperidin-1-yl} - (l-methyl-cyclopropyl) - methanone The title compound from rac - {(3R, 4S) -4 - (3,4-dichloro-phenyl) -l- [l- (1 -methyl- cyclopropanecarbonyl) -piperidine-4- carbonyl] -pyrrolidin-3- yl} 4-fluoro-benzyl ester as an off-white foam. MS m / e: 590.2 [M] ^&lt; ⁺ & gt ^; .

Example  96

rac -1 - {(3R, 4S) -4- (4- Chloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine Yl} -3- (4- Fluoro - Phenyl )-One- methyl - Urea

4-Fluoroaniline (178 [mu] l, 1.86 mmol) was added very carefully to a solution of the triphosgene (110 mg, 0.37 mmol) in dichloromethane (2 mL) at 0 ° C. The resulting suspension was stirred for 15 min before N, N-diisopropylethylamine (381 [mu] l, 2.23 mmol) was added dropwise. The solution was stirred at ambient temperature for 4 h before a solution of rac- {4 - [(3S, 4R) -3- (4-chloro-phenyl) -4- methylamino-pyrrolidine- L- yl} - (1-methyl-cyclopropyl) -methanone (150 mg, 0.37 mmol). The resulting solution in microwave was irradiated at 80 ° C for 30 minutes, then diluted with ethyl acetate (15 mL) and washed with an aqueous solution of sodium carbonate (1M, 15 mL). The organic layer was separated, washed with brine (15 mL) and the aqueous layer was extracted with ethyl acetate (20 mL). The combined organic layers were dried over sodium sulfate and concentrated. Purification by chromatography (SiO ₂ , heptane: ethyl acetate: methanol = 80: 20: 0 to 0:90:10) afforded the title compound (190 mg, 95%) as an off-white foam. MS m / e: 541.3 [M] ^&lt; ⁺ & gt ^; .

Example  97

rac -1- (2- Cyclopropyl -Ethyl) -3 - {(3R, 4S) -4- (3,4- Dichloro - Phenyl ) -1- [1- (1-methyl-cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine Yl} -1,3- Dimethyl - Urea

To a solution of rac - {(3R, 4S) -4- (3,4-dichloro-phenyl) -l- [1- (1- methyl- cyclopropanecarbonyl) -piperidin- (2-cyclopropyl-ethyl) -methyl-amine (99 mg, 1.0 mmol) and N, N-diisopropylethylamine were added to a solution of 4- N-diisopropylethylamine (256, 1.50 mmol) was added. The solution was irradiated in microwave at 130 ° C for 900 seconds, then diluted with ethyl acetate (15 mL) and washed with an aqueous solution of sodium carbonate (1M, 15 mL). The organic layer was separated, washed with brine (15 mL) and the aqueous layer was extracted with ethyl acetate (20 mL). The combined organic layers were dried over sodium sulfate and concentrated. Purification by chromatography (SiO _2, ethyl acetate: methanol = 100: 0 to 85:15) to give the title compound (202 mg, 72%) as a white foam. MS m / e: 563.4 [M] ^&lt; ⁺ & gt ^; .

Example  98

rac - {(3R, 4S) -4- (3,4- Dichloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  3- Hydroxy -3- methyl - butyl ester

Methyl-1,3-butanediol was used in place of 2-cyclopropylethanol to give rac - {4 - [(3S, 4R) -3- (3,4 -dichloro-phenyl) -4-methylamino-pyrrolidine-1-carbonyl] -piperidin-1-yl} - (l-methyl-cyclopropyl) - methanone The title compound from rac - {(3R , 4S) -4- (3,4-dichloro-phenyl) -l- [l- (1 -methyl- cyclopropanecarbonyl) -piperidine- 4-carbonyl] -pyrrolidin- } -Methyl-carbamic acid 3-hydroxy-3-methyl-butyl ester as an off-white foam. MS m / e: 568.2 [M] ^&lt; ⁺ & gt ^; .

Example  99

rac {(3R, 4S) -4- (3,4- Dichloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4,4- Difluoro - Cyclohexylmethyl  Ester

Embodiment, instead of 2-cyclopropyl-ethanol In analogy to the synthesis procedure, described in 25 (4,4-difluoro-cyclohexyl) using methanol rac - {4 - [(3S , 4R) -3- ( - (1-methyl-cyclopropyl) -methanone was prepared the title compound rac {(4-chloro-phenyl) -4-methylamino-pyrrolidine- (3R, 4S) -4- (3,4-Dichloro-phenyl) -l- -Yl} -methyl-carbamic acid 4,4-difluoro-cyclohexylmethyl ester as off-white foam. MS m / e: 614.2 [M] ^&lt; ⁺ & gt ^; .

Example  100

{(3R, 4S) -4- (4- Chloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4,4,4- Trifluro - butyl ester

And

Example  101

{(3S, 4R) -4- (4- Chloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4,4,4- Trifluro - butyl ester

In analogy to the synthetic procedure described in example 44 (step c), using l- (l-methyl-cyclopropanecarbonyl) -piperidine-4-carboxylic acid instead of l-methylcyclopropane-l- The title compound, {(3R, 4S) -4-chloro-4- (4-chloro-phenyl) -pyrrolidin- -Piperidin-4-carbonyl] -pyrrolidin-3-yl} -methyl-carbamic acid ethyl ester was prepared from 4- (4-chloro-phenyl) 4,4-trifluoro-butyl ester and {(3S, 4R) -4- (4-chloro-phenyl) 4-carbonyl] -pyrrolidin-3-yl} -methyl-carbamic acid 4,4,4-trifluoro-butyl ester as a light brown gum. MS m / e: 558.1 [M] ^&lt; ⁺ & gt ^; . The racemate was subjected to column chromatography on chiral tops to give {(3R, 4S) -4- (4-chloro-phenyl) -1- [1- (1- methyl- cyclopropanecarbonyl) -piperidin- (MS (m / e): 558.1 [M] ^&lt; ⁺ & gt ^; ) as an off-white foam and {( 4-carbonyl] -pyrrolidin-3-yl} - (4-chloro-phenyl) Methyl-carbamic acid 4,4,4-trifluoro-butyl ester (MS (m / e): 558.1 [M] ⁺ ) as an off-white foam.

Example  102

rac - {(3R, 4S) -4- (3,4- Dichloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4,4- Difluoro - Cyclohexyl  Ester

Using 4,4-difluoro-cyclohexanol in place of 2-cyclopropylethanol, rac - {4 - [(3S, 4R) -3- (3,4 -dichloro-phenyl) -4-methylamino-pyrrolidine-1-carbonyl] -piperidin-1-yl} - (l-methyl-cyclopropyl) - methanone The title compound from rac - {(3R , 4S) -4- (3,4-dichloro-phenyl) -l- [l- (1 -methyl- cyclopropanecarbonyl) -piperidine- 4-carbonyl] -pyrrolidin- } -Methyl-carbamic acid 4,4-difluoro-cyclohexyl ester as an off-white foam. MS m / e: 600.2 [M] ^&lt; ⁺ & gt ^; .

Example  103

rac - {(3R, 4S) -4- (3,4- Dichloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Trifluoromethyl - Cyclohexyl  Ester

Rac - {4 - [(3S, 4R) -3, 4-trifluoromethylphenyl) cyclohexanol (cis / trans mixture) was obtained in analogy to the synthetic procedure described in example 25 using 4-trifluoromethylcyclohexanol - (l-methyl-cyclopropyl) -methanone was prepared from the title compound as a light yellow foam, MS (ISP) rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- Pyridin-3-yl} -methyl-carbamic acid 4-trifluoromethyl-cyclohexyl ester as an off-white foam. MS m / e: 632.2 [M] ^&lt; ⁺ & gt ^; .

Example  104

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (4- Cyano - Cyclohexanecarbonyl ) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

Was prepared in analogy to the synthetic procedure described in example 44 (step c) using 4-cyano-cyclohexanecarboxylic acid instead of 1-methylcyclopropane-l-carboxylic acid to give [(3S, 4R) -4- (4-chloro-phenyl) -l- (4-cyano-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester was prepared the title compound [ Cyclohexanecarbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester as an off-white foam. MS m / e: 484.2 [M + H] &lt; ⁺ &gt;.

Example  105

{(3S, 4R) -4- (3,4- Dichloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  One- methyl - Cyclopropylmethyl  Ester

And

Example  106

{(3R, 4S) -4- (3,4- Dichloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  One- methyl - Cyclopropylmethyl  Ester

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- (3R, 4S) -4- (3,4-Dichloro-phenyl) -l-methyl-carbamic acid l- methyl- cyclopropylmethyl ester was prepared from 3- Methyl) -carbamic acid methyl ester (MS (m / e), was prepared in accordance with the general method of example 1 from l- (l-methyl-cyclopropanecarbonyl) -piperidine- e): 550.4 [M] <^+> ) as a white foam and {(3S, 4R) -4- (3,4- (MS / m): 550.4 [M] ^&lt; ⁺ & gt ^; ) as a white foam Respectively.

Example  107

{(3R, 4S) -4- (3,4- Dichloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Trifluoromethyl - Cyclohexyl  Ester

And

Example  108

{(3S, 4R) -4- (3,4- Dichloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Trifluoromethyl - Cyclohexyl  Ester

rac - {(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- (3S, 4R) -4- (3,4-dichloro-phenyl) - &lt; RTI ID = 0.0 & 4-carbonyl] -pyrrolidin-3-yl} -methyl-carbamic acid 4-trifluoromethyl-cyclohexyl ester (prepared from 1- MS (m / e): 632.2 [M] <^+> ) as an off-white foam and {(3S, 4R) -4- (3,4- carbonyl) -piperidin-4-carbonyl] -pyrrolidin-3-yl} -methyl-carbamic acid 4-trifluoromethyl-cyclohexyl ester (MS (m / e): 632.2 [m] + ) As an off-white foam.

Example  109

{(3S, 4R) -4- (4- Chloro - Phenyl ) -1- [1- (1,1- Dioxo - Hexahydro -1λ ⁶ - Thiopyran -4-yl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

In analogy to the synthetic procedure described in example 44 (step c), l- (l, l-dioxo-hexahydro-l [lambda] ⁶ -thiopyran-4-yl) - (4-chloro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester was prepared from [(3S, 4R) -4- {(3S, 4R) -4- ( 4- chloro-phenyl) -1- [1- (1, 1-dioxo-hexahydro--1λ ^{6-thiopyran-4-yl)} -piperidin-4 Carbonyl] -pyrrolidin-3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester as an off-white foam. MS m / e: 592.2 [M] ^&lt; ⁺ & gt ^; .

Example  110

{(3S, 4R) -4- (4- Chloro - Phenyl ) -1- [1- (6- Chloro - Pyridazine Yl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

Was prepared using 1- (6-chloro-3-pyridazinyl) -4-piperidinecarboxylic acid instead of 1-methylcyclopropane-l-carboxylic acid to give [ (4R, 4R) -4- (4-chloro-phenyl) -pyrrolidin- -Pyrrolidin-3-yl} -methyl-carbamic acid 4-fluoro-4-fluoro-pyridin- Phenyl ester as an off-white foam. MS m / e: 572.2 [M] ^&lt; ⁺ & gt ^; .

Example  111

rac - {(3R, 4S) -4- (3,4- dichloro-phenyl) -1- [1- (1-cyclopenten one propane-carbonyl) -piperidine-4-carbonyl] -pyrrolidin Pyridin- 3 - yl} -methyl - carbamic acid 3,3 -difluoro - cyclopentylmethyl ester

Embodiment, instead of 2-cyclopropyl-ethanol In analogy to the synthesis procedure, described in 25 (3,3-difluoro-cyclopentyl) - methanol using rac - {4 - [(3S , 4R) -3- ( - (1-methyl-cyclopropyl) -methanone was prepared the title compound, rac - (2-methyl-pyridin- [(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- 3-yl} -methyl-carbamic acid 3,3-difluoro-cyclopentylmethyl ester as colorless oil. MS m / e: 600.2 [M] ^&lt; ⁺ & gt ^; .

Example  112

{(3S, 4R) -4- (4- Chloro - Phenyl ) -1- [1- ( Tetrahydro -Pyran-4-yl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

In analogy to the synthetic procedure described in example 44 (step c), using 1- (tetrahydro-pyran-4-yl) -piperidine-4-carboxylic acid instead of 1- methylcyclopropane- (4R, 4R) -4- (4-chloro-phenyl) -pyrrolidin- Yl) -pyrrolidin-3-yl} -methyl-carbamic acid 4-fluoro-pyrrolidine- Phenyl ester as a white solid. MS m / e: 544.2 [M] ^&lt; ⁺ & gt ^; .

Example  113

{(3S, 4R) -4- (3,4- Dichloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  3- Bromo -4- Fluoro - Phenyl  Ester

Example 25 In analogy to the synthetic procedure described in this, by using the phenol with 3-bromo-4-fluoro instead of 2-cyclopropyl ethanol rac - {4 - [(3S , 4R) -3- (3,4- - (3S, 5S) -2-methyl-pyrrolidine-1-carbonitrile was prepared the title compound [ 4-carbonyl] -pyrrolidin-3-yl} -pyridin-4-yl) -Methyl-carbamic acid 3-bromo-4-fluoro-phenyl ester as colorless oil. MS m / e: 656.2 [M + H] &lt; ⁺ &gt;. This was subjected to column chromatography on chiral tops to give {(3S, 4R) -4- (3,4-dichloro-phenyl) -1- [1- (1- methyl- cyclopropanecarbonyl) -piperidin- Methyl-carbamic acid 3-bromo-4-fluoro-phenyl ester (MS (m / e): 656.1 [M + H] ⁺ ) as an off-white foam .

Example  114

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (3- Morpholine Yl- Propionate ) - Pyrrolidine Yl] -methyl- Carbamic acid  4- Fluoro - Phenyl  Ester

Was prepared in analogy to the synthetic procedure described in example 44 (step c) using 3-morpholin-4-yl-propionic acid instead of l-methylcyclopropane-l- (3S, 4R) -4- (4-chloro-phenyl) -1- (3-chloro- phenyl) -pyrrolidin-3- yl] -methyl- carbamic acid 4-fluoro-phenyl ester. -Morpholin-4-yl-propionyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester as a white solid. MS m / e: 490.2 [M + H] &lt; ⁺ &gt;.

Example  115

{(3S, 4R) -4- (4- Chloro - Phenyl ) -1- [1- (1,1- Dioxo - Tetrahydro -1λ ⁶ -Thiophen-3-yl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

In analogy to the synthetic procedure described in example 44 (step c), rac -l- (l, l-dioxo-tetrahydro- l [lambda] ⁶ -thiophen-3- yl) -piperidine- The title compound was prepared from [(3S, 4R) -4- (4-chloro-phenyl) -pyrrolidin-3- yl] -methyl- (4-chloro-phenyl) -l- (3-morpholin-4-yl-propionyl) -pyrrolidin-3- yl] -methyl-carbamic acid 4-fluoro-phenyl ester as a light yellow solid Respectively. MS m / e: 578.2 [M] ^&lt; ⁺ & gt ^; .

Example  116

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (4- Hydroxymethyl - Cyclohexanecarbonyl ) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

Was prepared in analogy to the synthetic procedure described in example 44 (step c) using 4-hydroxymethyl-1-cyclohexanecarboxylic acid instead of 1-methylcyclopropane-l-carboxylic acid to give [(3S, (4-chloro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester was prepared the title compound [ 4-hydroxymethyl-cyclohexanecarbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester as an off-white solid. MS m / e: 489.2 [M + H] &lt; ⁺ &gt;.

Example  117

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (4,4- Difluoro - Cyclohexanecarbonyl ) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

Was prepared in analogy to the synthetic procedure described in example 44 (step c) using 4,4-difluoro-cyclohexanecarboxylic acid instead of 1-methylcyclopropane-l-carboxylic acid to give [(3S, 4R) -4- (4-chloro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester was prepared the title compound [ 4,4-difluoro-cyclohexanecarbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester as an off-white solid. MS m / e: 494.2 [M] ^&lt; ⁺ & gt ^; .

Example  118

{(3S, 4R) -4- (4- Chloro - Phenyl ) -1- [1- (6- methyl - Pyridazine Yl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

(6-methyl-pyridazin-3-yl) -piperidine-4-carboxylic acid was used instead of 1-methylcyclopropane-l-carboxylic acid in analogy to the synthetic procedure described in example 44 The title compound was prepared from [(3S, 4R) -4- (4-chloro-phenyl) -pyrrolidin-3- yl] -methyl- (4-chloro-phenyl) -l- (4-hydroxymethyl-cyclohexanecarbonyl) -pyrrolidin-3- yl] -methyl- carbamic acid 4-fluoro-phenyl ester as an off-white solid. MS m / e: 552.1 [M] ^&lt; ⁺ & gt ^; .

Example  119

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] &lt; / RTI & Epithe 4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  Tert-butyl ester

a) [(3S, 4R) -1- benzyl-4- (4-chloro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid tert-butyl ester

To a solution of [(3S, 4R) -l-benzyl-4- (4-chloro-phenyl) -pyrrolidin-3- yl] -methyl- amine (4.42 g, 13 mmol) in dichloromethane Was added triethylamine (5.72 mL, 41 mmol), 4-dimethylaminopyridine (251 mg, 2 mmol) and di-tert-butyl-dicarbonate (4.92 g, 23 mmol). The resulting solution was stirred at ambient temperature for 20 hours and then diluted with water (30 mL). The organic layer was washed with water (30 mL) and the combined aqueous layers were extracted with dichloromethane (60 mL). Dry over sodium sulfate and concentrate to give the title compound (7.94 g, 96%) as a brown oil. MS m / e: 345.3 [M-tert-Butyl] ⁺ .

b) [(3S, 4R) -4- (4 -Chloro - phenyl ) -pyrrolidin- 3- yl] -methyl - carbamic acid tert- butyl ester

In analogy with the synthesis procedure described in Example 1 (step e), rac - [(3R , 4S) -1- benzyl-4- (3,4-dichloro-phenyl) -pyrrolidin-3-yl] - (3S, 4R) -l-Benzyl-4- (4-chloro-phenyl) -pyrrolidin-3- yl] -methyl-carbamic acid tert- butyl ester Pyrrolidin-3-yl] -methyl-carbamic acid tert-butyl ester as an orange brown oil. MS m / e: 311.4 [M + H] &lt; ⁺ &gt;.

c) [(3S, 4R) -4- (4- chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro -2H- [1,2 '] bar two feet Li Yl-4-carbonyl) -pyrrolidin- 3 - yl] -methyl - carbamic acid tert-butyl ester

The title compound was prepared in analogy to the synthetic procedure described in example 44 (step c) from 5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 ' Yl] -methyl-carbamic acid tert-butyl ester was prepared from [(3S, 4R) -4- (4-chloro-phenyl) -pyrrolidin- (3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro- Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid tert-butyl ester as an orange oil. MS m / e: 524.3 [M] ^&lt; ⁺ & gt ^; .

Example  120

rac - [(3S, 4R) -1- (5'-tert- Butylcarbamoyl -3,4,5,6- Tetrahydro -2H- [1,2 '] Bipyridinyl -4-carbonyl) -4- (4- Chloro - Phenyl ) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - phenyl ester

a) rac - [(3S, 4R) -4- (4 -Chloro - phenyl ) -1- (5'- cyano- 3,4,5,6- tetrahydro- 2H- [ Pyridin-4-carbonyl) -pyrrolidin- 3 - yl] -methyl - carbamic acid tert-butyl ester

In analogy to the synthetic procedure described in example 1 (step f), instead of l- (l-methyl-cyclopropanecarbonyl) -piperidine-4-carboxylic acid, 5'-cyano- -tetrahydro -2H- [1,2 '] by using the one-4-carboxylic acid bipyridinyl rac - [(3R, 4S) -4- (3,4- dichloro-phenyl) -pyrrolidin-3 yl] -methyl-carbamic acid tert-butyl ester in place of rac - [(3R, 4S) -4- (4- chloro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid tert-butyl Ester was prepared the title compound rac - [(3S, 4R) -4- (4-chloro-phenyl) -l- (5 ' -cyano-3,4,5,6-tetrahydro- ] Bipyridinyl-4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid tert-butyl ester as an orange oil. MS m / e: 524.3 [M] ^&lt; ⁺ & gt ^; .

b) rac - 4 - [( 3R, 4S) -3- (4- chloro-phenyl) -4-methylamino-pyrrolidine-1-carbonyl] 3,4,5,6-te Tra dihydro- 2H- [1,2 &apos;] bipyridinyl-5 & apos; -carbonitrile

In analogy to the synthetic procedure described in example 2 (step a), rac - {(3R, 4S) -4- (3,4-dichloro- phenyl) yl) -piperidine-4-carbonyl] -pyrrolidin-3-yl} -methyl-carbamic acid tert-butyl ester in place of rac - [(3S, 4R) -4- (4- chloro-phenyl ) - 1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl-4-carbonyl) -pyrrolidin- -carbamic acid tert-butyl ester The title compound from rac - 4 - [(3R, 4S ) -3- (4- chloro-phenyl) -4-methylamino-pyrrolidine-1-carbonyl] -3,4 , 5,6-tetrahydro-2H- [1,2 '] bipyridinyl-5'-carbonitrile as a light yellow solid. MS m / e: 424.3 [M + H] &lt; ⁺ &gt;.

c) rac - [(3S, 4R) -1- (5'-3 -tert-butyl-carbamoyl-3,4,5,6-tetrahydro -2H- [1,2 '] bipyridinyl-4-carbonyl yl) -4- (4-chloro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester

4- (3S, 4R) -3- (3,4-Dichloro-phenyl) - lH-pyrrolo [2,3-d] pyrimidine-4- carboxamide using 4- fluorophenyl chloroformate in analogy to the synthetic procedure described in example 2 4-methylamino-pyrrolidine-1-carbonyl] -piperidin-1-yl} - (l-methyl-cyclopropyl) -methanone in place of rac -4 - [(3R, 4S ) -3 - (4-chloro-phenyl) -4-methylamino-pyrrolidine- 1-carbonyl] -3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- The title compound, rac - [(3S, 4R) -1- (5'-tert-butylcarbamoyl-3,4,5,6-tetrahydro-2H- [ 4-carbonyl) -4- (4-chloro-phenyl) -pyrrolidin-3-yl] -methyl- carbamic acid 4-fluoro-phenyl ester as a white solid as a byproduct. MS m / e: 635.2 [MH] ^&lt;&quot;&gt;.

Example  121

rac - [(3S, 4R) -1- (5'-3 -tert-butyl-carbamoyl-3,4,5,6-tetrahydro -2H- [1,2 '] bipyridinyl-4-carbonyl) 4- (4-chloro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-trifluoromethyl-cyclohexyl ester

a) rac - [(3S, 4R) -4- (4 -Chloro - phenyl ) -1- (5'- cyano- 3,4,5,6- tetrahydro- 2H- [ Pyridin-4-carbonyl) -pyrrolidin- 3 - yl] -methyl - carbamic acid tert-butyl ester

In analogy to the synthetic procedure described in example 1 (step f), instead of l- (l-methyl-cyclopropanecarbonyl) -piperidine-4-carboxylic acid, 5'-cyano- -tetrahydro -2H- [1,2 '] by using the one-4-carboxylic acid bipyridinyl rac - [(3R, 4S) -4- (3,4- dichloro-phenyl) -pyrrolidin-3 yl] -methyl-carbamic acid tert-butyl ester in place of rac - [(3R, 4S) -4- (4- chloro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid tert-butyl Ester was prepared the title compound rac - [(3S, 4R) -4- (4-chloro-phenyl) -l- (5 ' -cyano-3,4,5,6-tetrahydro- ] Bipyridinyl-4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid tert-butyl ester as an orange oil. MS m / e: 524.3 [M] ^&lt; ⁺ & gt ^; .

b) rac -4 - [(3R , 4S) -3- (4- chloro-phenyl) -4-methylamino-pyrrolidine-1-carbonyl] 3,4,5,6-te Tra dihydro- 2H- [1,2 &apos;] bipyridinyl-5 & apos; -carbonitrile

In analogy to the synthetic procedure described in example 2 (step a), rac - {(3R, 4S) -4- (3,4-dichloro- phenyl) (3S, 4R) -4- (4-chloro-phenyl) -piperidine-4-carbonyl] -pyrrolidin-3- yl} -methylcarbamic acid tert- butyl ester ) - 1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl-4-carbonyl) -pyrrolidin- - carbamic acid tert-butyl ester, the title compound rac-4 - [(3R, 4S) -3- (4-chloro-phenyl) -4-methylamino-pyrrolidine- , 5,6-tetrahydro-2H- [1,2 '] bipyridinyl-5'-carbonitrile as a light yellow solid. MS m / e: 424.3 [M + H] &lt; ⁺ &gt;.

c) rac - [(3S, 4R) -1- (5'-3 -tert-butyl-carbamoyl-3,4,5,6-tetrahydro -2H- [1,2 '] bipyridinyl-4-carbonyl yl) -4- (4-chloro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-trifluoromethyl-cyclohexyl ester

Example 25 4-trifluoromethyl instead of 2-Cyclopropyl analogy to the synthesis procedure, described in ethanol methyl- using cyclohexanol (cis / trans mixture) rac - {4 - [( 3S, 4R) -3 - (l-methyl-cyclopropyl) -methanone was prepared in analogy to the procedure described for the preparation of Example 1c but using rac (3-chloro-phenyl) -4-methylamino-pyrrolidine- -4 - [(3R, 4S) -3- (4-chloro-phenyl) -4-methylamino-pyrrolidine- 1-carbonyl] -3,4,5,6-tetrahydro-2H- [ , 2 '] bipyridinyl-5'-carbonitrile The title compound, rac - [(3S, 4R) -1- (5'-tert-Butylcarbamoyl-3,4,5,6-tetrahydro- - [l, 2 '] bipyridinyl-4-carbonyl) -4- (4-chloro-phenyl) -pyrrolidin-3- yl] -methyl- carbamic acid 4- trifluoromethyl- cyclohexyl ester As an off-white foam. MS m / e: 692.3 [M] ^&lt; ⁺ & gt ^; .

Example  122

[(3R, 4S) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] &lt; / RTI & Epithe 4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

rac - [(3R, 4S) -4- (4-Chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [ -4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester was subjected to column chromatography to give [(3R, 4S) -4- Phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl-4-carbonyl) -pyrrolidin- Methyl-carbamic acid 4-fluoro-phenyl ester (MS (m / e): 562.2 [M] ⁺ ) as an off-white foam.

Example  123

{(3S, 4R) -4- (3,4- Dichloro - Phenyl ) -1- [1- ( Tetrahydro -Pyran-4-yl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Trifluoromethyl - Cyclohexyl  Ester

In analogy to the synthetic procedure described in example 44 (step c), using 1- (tetrahydro-pyran-4-yl) -piperidine-4-carboxylic acid instead of 1- methylcyclopropane- (3S, 4R) -4- (3,4-Dichloro-phenyl) -pyrrolidin-3- yl] -methyl-carbamic acid 4- (3S, 4R) -4- (3, 4-dichloro-phenyl) -pyrrolidin-3- yl] -methyl-carbamic acid 4- trifluoromethyl- cyclohexyl ester was prepared the title compound { Yl) -pyrrolidin-3-yl} -methyl-carbamic acid 4-trifluoro-pyridin-3- Lt; / RTI &gt; cyclohexyl ester as an off-white foam. MS m / e: 634.2 [M] ^&lt; ⁺ & gt ^; .

Example  124

rac - [(3S, 4R) -1- (5'-tert- Butylcarbamoyl -3,4,5,6- Tetrahydro -2H- [1,2 '] Bipyridinyl -4-carbonyl) -4- (4- Chloro - Phenyl ) - Pyrrolidine -3 days]- methyl - Carbamic acid  4,4,4- Trifluro - butyl ester

In analogy to the synthetic procedure described in example 25, by using 4,4,4-trifluoro-l-butanol instead of 2-cyclopropyl ethanol, rac - {4 - [(3S, 4R) -3- , 4-dichloro-phenyl) -4-methylamino-pyrrolidine-1-carbonyl] -piperidin-1-yl} - (l-methyl-cyclopropyl) -methanone in place of rac-4- [(3R, 4S) -3- (4-chloro-phenyl) -4-methylamino- pyrrolidine- 1-carbonyl] -3,4,5,6-tetrahydro- ] Bipyridinyl-5'-carbonitrile The title compound, rac- [(3S, 4R) -l- (5'-tert- butylcarbamoyl-3,4,5,6-tetrahydro- , 2 '] bipyridinyl-4-carbonyl) -4- (4-chloro-phenyl) -pyrrolidin-3- yl] -methyl- carbamic acid 4,4,4- trifluoro- As a by-product brown oil. MS m / e: 651.2 [MH] ^&lt;&quot;&gt;.

Example  125

[(3R, 4S) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] &lt; / RTI & Epithe 4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Trifluoromethyl - cyclohexyl ester

And

Example  126

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] &lt; / RTI & Epithe 4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Trifluoromethyl - cyclohexyl ester

Example 25 4-trifluoromethyl instead of 2-Cyclopropyl analogy to the synthesis procedure, described in ethanol methyl- using cyclohexanol (cis / trans mixture) rac - {4 - [( 3S, 4R) -3 - (l-methyl-cyclopropyl) -methanone was prepared in analogy to the procedure described for the preparation of Example 1c but using rac (3-chloro-phenyl) -4-methylamino-pyrrolidine- -4 - [(3R, 4S) -3- (4-chloro-phenyl) -4-methylamino-pyrrolidine- 1-carbonyl] -3,4,5,6-tetrahydro-2H- [ , 2 '] bipyridinyl-5'-carbonitrile The title compound, rac - [(3R, 4S) -4- Pyridin-4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-trifluoromethyl-cyclohexyl ester as a colorless oil . MS m / e: 618.2 [M] ^&lt; ⁺ & gt ^; . This was subjected to column chromatography on chiral tops to give [(3S, 4R) -4- (4-chloro-phenyl) -1- (5 ' -cyano-3,4,5,6-tetrahydro-2H- [ Methyl) -carbamic acid 4-trifluoromethyl-cyclohexyl ester (MS (m / e): 617.4 [M] ^&lt; ⁺ & gt ^; ) As a yellow solid and [(3R, 4S) -4- (4-chloro-phenyl) -1- (5 ' -cyano-3,4,5,6-tetrahydro- Yl] -methyl-carbamic acid 4-trifluoromethyl-cyclohexyl ester (MS (m / e): 617.4 [M] <^+> ) was obtained as yellow Obtained as a solid.

Example  127

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] bipyridinyl-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  4,4,4- Trifluro - butyl ester

And

Example  128

[(3R, 4S) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] &lt; / RTI & Epithe 4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  4,4,4- Trifluro - butyl ester

In analogy to the synthetic procedure described in example 25, by using 4,4,4-trifluoro-l-butanol instead of 2-cyclopropyl ethanol, rac - {4 - [(3S, 4R) -3- 4- (4-Chloro-phenyl) -4-methylamino-pyrrolidine- 1-carbonyl] -piperidin- 1 -yl} - [(3R, 4S) -3- (4-chloro-phenyl) -4-methylamino- pyrrolidine- 1-carbonyl] -3,4,5,6-tetrahydro- ] Bipyridinyl-5'-carbonitrile The title compound, rac - [(3R, 4S) -4- (4-chloro-phenyl) -l- (5'-cyano-3,4,5,6-tetra Pyridin-4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4,4,4-trifluoro-butyl ester as a yellow solid Respectively. MS m / e: 578.4 [M + H] &lt; ⁺ &gt;. This was subjected to column chromatography on chiral tops to give [(3S, 4R) -4- (4-chloro-phenyl) -1- (5 ' -cyano-3,4,5,6-tetrahydro-2H- [ Methyl-carbamic acid 4,4,4-trifluoro-butyl ester (MS (m / e): 577.2 [M ] ⁺ ) Was obtained as a yellow foam and [(3R, 4S) -4- (4-chloro-phenyl) -1- (5 ' -cyano-3,4,5,6-tetrahydro- Methyl) -carbamic acid 4,4,4-trifluoro-butyl ester (MS (m / e): 577.2 [M] ⁺ ) ^& Lt; / RTI &gt; as a yellow foam.

Example  129

{(3S, 4R) -4- (4- Fluoro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

a) rac- (3S, 4R) -l-Benzyl-3- (4- fluoro - phenyl ) -4-nitro- pyrrolidine

Fluoro-4 - ((E) -2-nitro-vinyl) -benzene was prepared in analogy to the synthetic procedure described in example 1 (step a), instead of l, 2- 2-nitro-vinyl) benzene the title compound, rac - (3S, 4R) -1- benzyl-3- (4-fluoro-to give the pyrrolidine as a light yellow oil-phenyl) -4-nitro. MS m / e: 301.2 [M + H] &lt; ⁺ &gt;.

b) rac - (3R, 4S ) -1- benzyl-4- (4-fluoro-phenyl) -pyrrolidin-3-ylamine

In analogy with the synthesis procedure described in Example 1 (step b), rac - (3R, 4S) -1- benzyl-3- (3,4-dichloro-phenyl) -4-nitro-blood instead of pyrrolidine rac - (3S, 4R) -1- benzyl-3- (4-fluoro-phenyl) -4-nitro-pyrrolidine The title compound, rac from Dean - (3R, 4S) -1- benzyl-4- (4-fluoro Chloro-phenyl) -pyrrolidin-3-ylamine as a light brown oil. MS m / e: 271.3 [M + H] &lt; ⁺ &gt;.

c) rac - [(3R, 4S) -1- benzyl-4- (4-fluoro-phenyl) -pyrrolidin-3-yl] -methyl-amine

(3S, 4R) -l-Benzyl-4- (3,4-dichloro-phenyl) -pyrrolidin-3-ylamine instead of rac- rac - (3R, 4S) -1- benzyl-4- (4-fluoro-phenyl) -pyrrolidine The title compound from 3-ylamine rac - [(3R, 4S) -1- benzyl-4- ( 4-fluoro-phenyl) -pyrrolidin-3-yl] -methyl-amine as a light brown oil. MS m / e: 285.2 [M + H] &lt; ⁺ &gt;.

d) rac - [(3R, 4S) -1- benzyl-4- (4-fluoro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluorine-phenyl ester

In analogy to the synthetic procedure described in example 2 (step b), rac - {4 - [(3S, 4R) -3- (3,4-Dichloro- phenyl) -4- methylamino-pyrrolidin- - carbonyl] -piperidin-1-yl} - (l-methyl-cyclopropyl) -methanone in place of rac - [(3R, 4S) -1-benzyl-4- (4-fluoro-phenyl) -pyrrolidin-3-yl] - amine The title compound, rac-methyl [(3R, 4S) -1- benzyl-4- (4-fluoro-phenyl) -pyrrolidin-3-yl] -methyl -Carbamic acid 4-fluoro-phenyl ester as a yellow oil. MS m / e: 423.2 [M + H] &lt; ⁺ &gt;.

e) rac - [(3R, 4S) -4- ( 4-fluoro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester

In analogy with the synthesis procedure described in Example 1 (step e), rac - [(3R , 4S) -1- benzyl-4- (3,4-dichloro-phenyl) -pyrrolidin-3-yl] - (4-fluoro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid tert-butyl ester was prepared in analogy to the procedure described for the synthesis of rac - [(3R, Fluoro-phenyl ester was obtained as a brownish brown color from the title compound rac - [(3R, 4S) -4- (4-fluoro- phenyl) -pyrrolidin- As an oil which was used without further purification.

f) rac - {(3R, 4S) -4- (4- fluoro-phenyl) -1- [1- (1-methyl-cyclopropane-carbonyl) -piperidine-4-carbonyl] -pyrrolidin Pyridin- 3 - yl} -methyl - carbamic acid 4- fluoro - phenyl ester

In analogy to the synthetic procedure described in example 1 (step f), rac - [(3R, 4S) -4- (3,4-dichloro- phenyl) -pyrrolidin- The title compound, was prepared from rac - [(3R, 4S) -4- (4-fluoro-phenyl) -pyrrolidin-3- yl] -methyl-carbamic acid 4-fluoro- rac - {(3R, 4S) -4- (4-fluoro-phenyl) -l- 3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester as a light brown semi solid. MS m / e: 526.4 [M + H] &lt; ⁺ &gt;.

g) {(3S, 4R) -4- ( 4-fluoro-phenyl) -1- [1- (1-methyl-cyclopropane-carbonyl) -piperidine-4-carbonyl] -pyrrolidin- 3-yl} -methyl - carbamic acid 4- fluoro - phenyl ester

rac - {(3R, 4S) -4- (4-fluoro-phenyl) -l- 3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester was chromatographed on chiral top to give {(3S, 4R) -4- (4-fluoro- Methyl) -carbamic acid 4-fluoro-phenyl ester (MS (m / e): 526.4 [M + &Gt; H] &lt; ⁺ &gt;) as a white foam.

Example  130

{(3R, 4S) -4- (4- Fluoro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

rac - {(3R, 4S) -4- (4-fluoro-phenyl) -l- 3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester was subjected to column chromatography to give {(3R, 4S) -4- (4- fluoro- Methyl) -carbamic acid 4-fluoro-phenyl ester (MS (m / e): 526.4 [M + &Gt; H] &lt; ⁺ &gt;) as a colorless waxy solid.

Example  131

[(3S, 4R) -1- (5 ' - Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] Bipyridinyl -4-carbonyl) -4- (4- Fluoro - Phenyl ) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

And

Example  132

[(3R, 4S) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] Bipyridinyl -4-carbonyl) -4- (4- Fluoro - Phenyl ) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

The title compound was prepared in analogy to the synthetic procedure described in example 44 (step c) from 5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 ' Yl ] -methyl-carbamic acid 4-fluoro-phenyl} -piperidine-4-carboxylic acid was prepared from rac - [(3R, Ester was prepared the title compound rac - [(3R, 4S) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -4- (4-fluoro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester as brown semisolid. MS m / e: 562.1 [M] ^&lt; ⁺ & gt ^; . The racemate was then subjected to column chromatography on chiral tops to give - [(3S, 4R) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [ Fluoro-phenyl ester (MS (m / e): 546.3 &lt; RTI ID = 0.0 &gt; [ M + H] ⁺ ) as a yellow waxy solid and [- (3R, 4S) -1- (5'- Fluoro-phenyl ester (MS (m / e): 546.3 &lt; RTI ID = 0.0 &gt; [ M + H] &lt; ⁺ &gt;) as a yellow waxy solid.

Example  133

4 - {(3R, 4S) -3- (4- Chloro - Phenyl ) -4 - [(4- Fluoro - Phenoxycarbonyl ) - methyl -Amino] -pyrrolidine-l-carbonyl} -piperidin-l- Carboxylic acid  Tert-butyl ester

In analogy to the synthetic procedure described in example 44 (step c), using piperidine-l, 4-dicarboxylic acid mono-tert-butyl ester instead of l-methylcyclopropane-l- (3S, 4R) -4- (4-tert-butoxycarbonylamino) -acetic acid was used in the place of 4-fluoro- Chloro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester was prepared the title compound 4 - {(3R, (4-Fluoro-phenoxycarbonyl) -methyl-amino] -pyrrolidine-l-carbonyl} -piperidine-l-carboxylic acid tert- butyl ester as a light brown gum. MS m / e: 560.3 [M] ^&lt; ⁺ & gt ^; .

Example  134

{(3S, 4R) -4- (4- Chloro - Phenyl ) -1- [1- (5- methyl - [1,3,4] Oxadiazole -2-yl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

The title compound was prepared in analogy to the synthetic procedure described in example 44 (step c) from l- (5-methyl- [1,3,4] oxadiazol-2-yl) -pyridine instead of 1- methylcyclopropane- Pyrrolidine-4-carboxylic acid in place of [(3S, 4R) -4- (3,4-dichloro-phenyl) -pyrrolidin- Fluoro-phenyl ester was prepared the title compound 4 - {(3R, 4S) - (4-chloro-phenyl) -pyrrolidin- Carboxylic acid tert-butoxycarbonylamino-pyrrolidine-l-carbonyl} -piperidine-l-carboxylic acid tert- Butyl ester as an off-white foam. MS m / e: 542.3 [M] ^&lt; ⁺ & gt ^; .

Example  135

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (piperidine-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

In analogy to the synthetic procedure described in example 2 (step a), rac - {(3R, 4S) -4- (3,4-dichloro- phenyl) (3R, 4S) -3- (4-chloro-phenyl) -piperidine-4-carbonyl] -pyrrolidine-3- carboxylic acid tert- Carboxylic acid tert-butyl ester was prepared the title compound [(3S (4-fluoro-phenoxycarbonyl) -methyl-amino] -pyrrolidine- 1-carbonyl} -piperidine- -Pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester as a light brown foam &Lt; / RTI &gt; MS m / e: 460.4 [M + H] &lt; ⁺ &gt;.

Example  136

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] bipyridinyl-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  Ethyl ester

a) 4 - [(3R, 4S) -3- (4- chloro-phenyl) -4-methylamino-pyrrolidine-1-carbonyl] 3,4,5,6-te Tra dihydro -2H- [L, 2 '] bipyridinyl- 5'- carbonitrile

To a solution of [(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [ Butyl ester (3.20 g, 6.12 mmol) in dichloromethane (5 mL) was added trifluoroacetic acid (4.7 mL , 61.2 mmol) and the reaction mixture was stirred at this temperature for 4 hours. After concentration, the residue was dissolved in ethyl acetate and washed with aqueous sodium carbonate (20%). The organic layer was dried over sodium sulfate and concentrated to give the title compound (1.90 g, 73%) as a pale yellow foam. MS m / e: 424.2 [M + H] &lt; ⁺ &gt;.

b) [(3S, 4R) -4- (4- chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro -2H- [1,2 '] bar two feet Li Yl-4-carbonyl) -pyrrolidin- 3 - yl] -methyl - carbamic acid ethyl ester

To a solution of 4 - [(3R, 4S) -3- (4-chloro-phenyl) -4-methylamino-pyrrolidine- 1-carbonyl] -3,4,5,6- (13 [mu] L, 0.09 mmol) and ethyl chloroformate (9 [mu] L, 0.09 mmol) were added to a solution of 3-methoxy- tetrahydro-2H- [1,2 '] bipyridinyl-5'-carbonitrile mmol) were added and the reaction mixture was stirred at ambient temperature for 3 hours. Concentrated and purified by chromatography to give the title compound (20 mg, 57%) as a colorless foam. MS m / e: 496.4 [M] ^&lt; ⁺ & gt ^; .

Example  137

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] &lt; / RTI & Epithe 4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  Isopropyl ester

In analogy to the synthetic procedure described in example 136, 4 - [(3R, 4S) -3- (4-chloro-phenyl) -4-methylamino-pyridine-4- carboxamide using isopropyl chloroformate instead of ethyl chloroformate. Carbonyl] -3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl-5'-carbonitrile was prepared the title compound [(3S, 4R) -4- 4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl-4-carbonyl) -pyrrolidin- -Yl] -methyl-carbamic acid isopropyl ester as colorless foam. MS m / e: 510.4 [M] ^&lt; ⁺ & gt ^; .

Example  138

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] &lt; / RTI & Epithe 4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  Profile ester

In analogy to the synthetic procedure described in example 136, 4 - [(3R, 4S) -3- (4-chloro-phenyl) -4-methylamino-pyrrolidine using propyl chloroformate instead of ethyl chloroformate Carbonyl] -3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl-5'-carbonitrile was prepared the title compound [(3S, 4R) -4- - chloro-phenyl) -l- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl-4-carbonyl) -pyrrolidin- Yl-methyl-carbamic acid propyl ester as colorless foam. MS m / e: 510.4 [M] ^&lt; ⁺ & gt ^; .

Example  139

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] &lt; / RTI & Epithe 4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  Isobutyl ester

In analogy to the synthetic procedure described in example 136, 4 - [(3R, 4S) -3- (4-chloro-phenyl) -4-methylamino-pyridin- Carbonyl] -3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl-5'-carbonitrile was prepared the title compound [(3S, 4R) -4- 4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl-4-carbonyl) -pyrrolidin- -Yl] -methyl-carbamic acid isobutyl ester as colorless foam. MS m / e: 524.5 [M] ^&lt; ⁺ & gt ^; .

Example  140

{(3S, 4R) -4- (4- Chloro - Phenyl ) -1- [1- (6- Cyano - Pyridazine Yl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

To a solution of [(3S, 4R) -4- (4-chloro-phenyl) -l- (piperidine-4-carbonyl) -pyrrolidin- 6-chloro-3-pyridazinecarbonitrile (67 mg, 0.48 mmol) and N, N-diisopropylethylamine (208, 1.21 mmol) were added to a solution of 4- . The resulting dark brown solution was stirred at 80 &lt; 0 &gt; C for 3 hours. After cooling to ambient temperature, the reaction mixture was diluted with ethyl acetate (15 mL) and washed with aqueous sodium carbonate (1M, 15 mL), water (15 mL) and brine (15 mL). The aqueous layer was extracted with ethyl acetate (15 mL) and the combined organic layers were dried over sodium sulfate. Concentrated, and chromatographed (SiO _2, heptane: ethyl acetate = 50:50 to 0: 100) to give the title compound (167 mg, 73%) as a white foam. MS m / e: 563.3 [M] ^&lt; ⁺ & gt ^; .

Example  141

{(3S, 4R) -4- (4- Chloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  Isobutyl ester

a) {(3S, 4R) -4- (4- chloro-phenyl) -1- [1- (1-cyclopenten one propane-carbonyl) -piperidin-4-O bonil] -pyrrolidin -3 - yl} -methyl - carbamic acid tert-butyl ester

(3S, 4R) -4- (4-chloro-phenyl) -pyrrolidine-3-carboxylic acid was prepared in analogy to the synthetic procedure described in example 44 (step c) using 1-methylcyclopropane- (3S, 4R) -4- (4-chloro-phenyl) -pyrrolidin-3- yl] -methyl-carbamic acid tert- butyl ester Ester was prepared the title compound {(3S, 4R) -4- (4-chloro-phenyl) -1- [1- (1- methyl- cyclopropanecarbonyl) -piperidin- Yl} -methyl-carbamic acid tert-butyl ester as an off-white foam. MS m / e: 504.2 [M] ^&lt; ⁺ & gt ^; .

b) Preparation of [(3R, 4S) -3- (4 -chloro - phenyl ) -4 -methylamino - pyrrolidin- 1 -yl] - [1- (1- methyl- cyclopropanecarbonyl) -piperidine -4-yl] -methanone

In analogy to the synthetic procedure described in example 2 (step a), rac - {(3R, 4S) -4- (3,4-dichloro- phenyl) (3S, 4R) -4- (4-chloro-phenyl) - piperidine-4-carbonyl] -pyrrolidin- The title compound was prepared from [(3R) -lH-indol-3-yl] -methylcarbamic acid tert- (4-chloro-phenyl) -4-methylamino-pyrrolidin- 1 -yl] -Methanone &lt; / RTI &gt; as a light yellow foam. MS m / e: 403.9 [M] ^&lt; ⁺ & gt ^; .

c) {(3S, 4R) -4- (4- chloro-phenyl) -1- [1- (1-cyclopenten one propane-carbonyl) -piperidine-4-carbonyl] -pyrrolidin -3 - yl} -methyl - carbamic acid isobutyl ester

In analogy to the synthetic procedure described in example 136, 4 - [(3R, 4S) -3- (4-chloro-phenyl) -4-methylamino-pyridin- Carbonyl] -3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl-5'-carbonitrile in place of [(3R, 4S) -3- -Methanone was prepared the title compound {(1-methyl-cyclopropanecarbonyl) -piperidin-4-yl] 4-carbonyl] -pyrrolidin-3-yl} - (4-chloro-phenyl) Methyl-carbamic acid isobutyl ester as a colorless foam. MS m / e: 504.2 [M] ^&lt; ⁺ & gt ^; .

Example  142

{(3S, 4R) -4- (4- Chloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  Profile ester

In analogy to the synthetic procedure described in example 136, 4 - [(3R, 4S) -3- (4-chloro-phenyl) -4-methylamino-pyrrolidine using propyl chloroformate instead of ethyl chloroformate Carbonyl] -3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl-5'-carbonitrile in place of [(3R, 4S) -3- -Methanone was prepared the title compound {(3S (4-chloro-phenyl) -4-methylamino-pyrrolidin- -Piperidin-4-carbonyl] -pyrrolidin-3-yl} -methyl- cyclopentanecarboxylic acid was prepared in accordance with the general method of example 1 from 4- (4-chloro-phenyl) -Carbamic acid propyl ester as colorless &lt; / RTI &gt; foam. MS m / e: 490.4 [M] ^&lt; ⁺ & gt ^; .

Example  143

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] &lt; / RTI & Epithe 4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid Cyclohexyl  Ester

(4S, 4R) -3- (3,4-Dichloro-phenyl) -4H-pyrrolo [2,3-d ] pyrimidin- 4 - [(3R, 4S) -3- (4-tert-butoxycarbonylamino) -piperidine-l- Chloro-phenyl) -4-methylamino-pyrrolidine-l-carbonyl] -3,4,5,6-tetrahydro-2H- [ [(3S, 4R) -4- (4-Chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro- 4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid cyclohexyl ester as colorless foam. MS m / e: 550.4 [M] ^&lt; ⁺ & gt ^; .

Example  144

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] &lt; / RTI & Epithe 4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  3,3,3- Trifluro -Profile ester

And

Example  145

[(3R, 4S) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] &lt; / RTI & Epithe 4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  3,3,3- Trifluro -Profile ester

Example In analogy to the procedure described in Synthesis 25, using 1-propanol instead of 3,3,3-trifluoro-2-cyclopropyl-ethanol rac - {4 - [(3S , 4R) -3- (3 4- (4-Chloro-phenyl) -4-methylamino-pyrrolidine- 1-carbonyl] -piperidin- 1 -yl} - [(3R, 4S) -3- (4-chloro-phenyl) -4-methylamino- pyrrolidine- 1-carbonyl] -3,4,5,6-tetrahydro- ] Bipyridinyl-5'-carbonitrile The title compound, rac - [(3R, 4S) -4- (4-chloro-phenyl) -l- (5'-cyano-3,4,5,6-tetra Pyrrolidin-3-yl] -methyl-carbamic acid 3,3,3-trifluoro-propyl ester as a colorless oil Respectively. MS m / e: 563.2 [M] ^&lt; ⁺ & gt ^; . This was subjected to column chromatography on chiral tops to give [(3S, 4R) -4- (4-chloro-phenyl) -1- (5 ' -cyano-3,4,5,6-tetrahydro-2H- [ , MS (m / e): 563.2 [M &lt; RTI ID = 0.0 &gt; ] ⁺ ) As a yellow solid and [(3R, 4S) -4- (4-chloro-phenyl) -1- (5 ' -cyano-3,4,5,6-tetrahydro- Methyl] -carbamic acid 3,3,3-trifluoro- propyl ester (MS (m / e): 563.2 [M] &lt; ⁺ ) ^& Lt; / RTI &gt; as a yellow foam.

Example  146

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (2,2- Dimethyl - Tetrahydro -Pyran-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

Was prepared in analogy to the synthetic procedure described in example 44 (step c) using 2,2-dimethyl-tetrahydro-2H-pyran-4-carboxylic acid instead of 1-methylcyclopropane-l- (3S, 4R) -4- (4-tert-butoxycarbonylamino) -acetic acid was used in the place of 4-fluoro- Chloro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester was prepared the title compound [(3S, 4R) -4- 2-Dimethyl-tetrahydro-pyran-4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester as an off-white foam. MS m / e: 489.3 [M + H] &lt; ⁺ &gt;.

Example  147

[(3S, 4R) -4- (4- Chloro - Phenyl )-One-( Tetrahydro - pyran-3-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

Was prepared in analogy to the synthetic procedure described in example 44 (step c) from [(3S, 4R) -4- (3-tert-butylpiperidine-l-carboxylic acid tert-butyl ester using rac-tetrahydro-pyran-3-carboxylic acid instead of 1-methylcyclopropane- (4-chloro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro- (4-chloro-phenyl) -l- (tetrahydro-pyran-3-carbonyl) -pyridin- ) -Pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester as an off-white foam. MS m / e: 461.2 [M + H] &lt; ⁺ &gt;.

Example  148

[(3S, 4R) -4- (4- Chloro - Phenyl )-One-( Tetrahydro - furan-3-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

(3S, 4R) -4- (3, &lt; / RTI &gt; 4R) -4- (4-chloro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester instead of [ 4- (4-chloro-phenyl) -l- (tetrahydro-furan-3-carbonyl) -piperidine- -Pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester as a light brown oil. MS m / e: 447.2 [M + H] &lt; ⁺ &gt;.

Example  149

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (3- Methoxy - Cyclobutanecarbonyl ) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

Was prepared in analogy to the synthetic procedure described in example 44 (step c) using 3-methoxycyclobutanecarboxylic acid instead of 1-methylcyclopropane-l-carboxylic acid to give [(3S, 4R) -4- -4-chloro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester instead of [ (3S, 4R) -4- (4-chloro-phenyl) -l- (3-methoxy-cyclobutanecarbonyl) -pyridin- 3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester as a light brown oil. MS m / e: 461.2 [M + H] &lt; ⁺ &gt;.

Example  150

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (1- Cyclopropyl -Piperidine-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

Was prepared in analogy to the synthetic procedure described in example 44 (step c) using 1-cyclopropyl-piperidine-4-carboxylic acid instead of 1- methylcyclopropane-l-carboxylic acid to give [(3S, (4-chloro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro- (4-chloro-phenyl) -l- (l-cyclopropyl-piperazin-l-yl) -pyrrolidin- 4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester as a white foam. MS m / e: 500.3 [M] ^&lt; ⁺ & gt ^; .

Example  151

3 - {(3R, 4S) -3- (4- Chloro - Phenyl ) -4 - [(4- Fluoro - Phenoxycarbonyl ) - methyl -Amino] -pyrrolidine-l-carbonyl} - Pyrrolidine -One- Carboxylic acid  Tert-butyl ester

Pyrrolidine-l, 3-dicarboxylic acid l-tert-butyl ester in place of 1-methylcyclopropane-l-carboxylic acid in analogy to the synthetic procedure described in example 44 (step c) (3S, 4R) -4- ((3S, 4R) -4- (3,4-Dichloro- phenyl) -pyrrolidin- 3-yl] -methyl-carbamic acid 4-fluoro- 4-chloro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester was prepared the title compound 3 - {(3R, - [(4-fluoro-phenoxycarbonyl) -methyl-amino] -pyrrolidine-l- carbonyl} -pyrrolidine- 1-carboxylic acid tert- butyl ester as a light yellow oil. MS m / e: 546.2 [M] ^&lt; ⁺ & gt ^; .

Example  152

{(3S, 4R) -4- (4- Chloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid Cyclohexyl  Ester

(4S, 4R) -3- (3,4-Dichloro-phenyl) -4H-pyrrolo [2,3-d ] pyrimidin- (3R, 4S) -3- (4-chloro-pyridin-2-ylmethyl) -piperidine-l- The title compound was prepared from {(3S, 4R (2R, 3R, 3R, 3R, 5R) Yl) -piperidin-4-carbonyl] -pyrrolidin-3-yl} -methyl-carbaldehyde Lt; / RTI &gt; acid ethyl ester as a colorless foam. MS m / e: 530.2 [M] ^&lt; ⁺ & gt ^; .

Example  153

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] bipyridinyl-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  One- Cyclopropyl -ethyl s foundation

Example 25 In analogy to the synthetic procedure described in this, by using 1-cyclopropyl-ethanol in place of 2-cyclopropyl ethanol rac - {4 - [(3S , 4R) -3- (3,4- dichloro-phenyl) 4 - [(3R, 4S) -3- (2-methyl-pyridin- Carbonyl] -3,4,5,6-tetrahydro-2H- [1,2 &apos;] bipyridinyl-5 ' -carbonitrile (5-cyano-3,4,5,6-tetrahydro-2H- [1,2 &apos;] bipyridine Yl-4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 1-cyclopropyl-ethyl ester as colorless foam. MS m / e: 536.3 [M] ^&lt; ⁺ & gt ^; .

Example  154

{(3S, 4R) -4- (4- Chloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  One- Cyclopropyl - ethyl ester

Example 25 In analogy to the synthetic procedure described in this, by using 1-cyclopropyl-ethanol in place of 2-cyclopropyl ethanol rac - {4 - [(3S , 4R) -3- (3,4- dichloro-phenyl) (3R, 4S) -3- (4-tert-butoxycarbonylamino-pyrrolidine-1-carbonyl) -piperidin- -Methanone was prepared the title compound {(3S (4-chloro-phenyl) -4-methylamino-pyrrolidin- -Piperidin-4-carbonyl] -pyrrolidin-3-yl} -methyl- cyclopentanecarboxylic acid was prepared in accordance with the general method of example 1 from 4- (4-chloro-phenyl) -Carbamic &lt; / RTI &gt; acid 1-cyclopropyl-ethyl ester as colorless foam. MS m / e: 516.5 [M] ^&lt; ⁺ & gt ^; .

Example  155

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] bipyridinyl-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid Oxetane Yl ester

In analogy to the synthetic procedure described in example 25, by using oxetan-3-ol instead of 2-cyclopropylethanol, rac- {4 - [(3S, 4R) -3- (3,4- ) - 4-methylamino-pyrrolidine-l-carbonyl] -piperidin- 1 -yl} - (1- methyl- cyclopropyl) (4-chloro-phenyl) -4-methylamino-pyrrolidine- 1-carbonyl] -3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl-5'- The title compound [(3S, 4R) -4- (4-chloro-phenyl) -1- (5'- Pyridin-4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid oxetan-3-yl ester as colorless foam. MS m / e: 524.4 [M] ^&lt; ⁺ & gt ^; .

Example  156

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] &lt; / RTI & Epithe 4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid Tetrahydro -Pyran-4-yl ester

Example 25 In analogy to the synthetic procedure described in this, by using tetrahydropyran-4-ol in place of 2-cyclopropyl ethanol rac - {4 - [(3S , 4R) -3- (3,4- dichloro- 4 - [(3R, 4S) -3-tert-butoxycarbonylamino-pyrrolidine-1-carbonyl] -piperidin- 1 -yl} - - (4-chloro-phenyl) -4-methylamino-pyrrolidine- 1-carbonyl] -3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- Carbonitrile was converted to the title compound [(3S, 4R) -4- (4-Chloro-phenyl) -1- (5 ' -cyano-3,4,5,6-tetrahydro- 4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid tetrahydro-pyran-4-yl ester as colorless foam. MS m / e: 552.4 [M] ^&lt; ⁺ & gt ^; .

Example  157

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] bipyridinyl-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  SE-butyl ester

In analogy to the synthetic procedure described in example 25, 2-butanol was used in place of 2-cyclopropylethanol to give rac - {4 - [(3S, 4R) -3- (3,4- 4 - [(3R, 4S) -3- (4-tert-butoxycarbonylamino) -piperidine-l- Chloro-phenyl) -4-methylamino-pyrrolidine-l-carbonyl] -3,4,5,6-tetrahydro-2H- [ [(3S, 4R) -4- (4-Chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro- 4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid tert-butyl ester as colorless foam. MS m / e: 524.4 [M] ^&lt; ⁺ & gt ^; .

Example  158

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] bipyridinyl-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  2,2,2- Trifluro - ethyl ester

(4S, 4R) -3- (3,4- dichloropyrimidin -4-yl) -ethanone using 2,2,2-trifluoroethanol instead of 2-cyclopropylethanol in analogy to the synthetic procedure described in example 25, 4 - [(3R, 4S) -7-chloro-phenyl] -4-methylamino-pyrrolidine- ) -3- (4-chloro-phenyl) -4-methylamino-pyrrolidine- 1-carbonyl] -3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- (5-cyano-3,4,5,6-tetrahydro-2H- [1, &lt; / RTI &gt; 2 '] bipyridinyl-4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 2,2,2-trifluoro-ethyl ester as colorless foam. MS m / e: 550.4 [M] ^&lt; ⁺ & gt ^; .

Example  159

[(3S, 4R) -1- (5 ' - Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] Bipyridinyl -4-carbonyl) -4- (3,4- Dichloro - Phenyl ) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Trifluoromethyl -four Cyclohexyl  Ester

a) ( 3,4 -Dichloro - phenyl ) -propionic acid ethyl ester

In analogy to the synthetic procedure described in example 89 (step a) from 3,4-dichloroiodobenzene instead of l-chloro-4-iodobenzene the title compound (3,4-dichloro-phenyl) Lt; / RTI &gt; acid ethyl ester as a brown solid. MS m / e: 244.0 [M + H] &lt; ⁺ &gt;.

b) 1- Benzyl-4- (3,4-dichloro-phenyl) -2,5-dihydro -1H- pyrrole-3-carboxylic acid

Prepared in analogy to the synthetic procedure described in example 89 (step b) from (3,4-dichloro-phenyl) -propionic acid ethyl ester instead of (4-chloro-phenyl) (3,4-dichloro-phenyl) -2,5-dihydro-lH-pyrrole-3-carboxylic acid as an off-white solid. MS m / e: 347.9 [MH] ^&lt;&quot;&gt;.

c) (3R, 4R) -1- benzyl-4- (3,4-dichloro-phenyl) -pyrrolidine-3-carboxylic acid

Was prepared in analogy to the synthetic procedure described in example 89 (step c) from 1-benzyl-4- (4-chloro-phenyl) -2,5-dihydro-lH-pyrrole- - (3,4-dichloro-phenyl) -2,5-dihydro-lH-pyrrole-3- ) -Pyrrolidine-3-carboxylic acid as light gray crystals (ee > 99.9% R, R (chiral HPLC)). MS m / e: 350.2 [M] ^&lt; ⁺ & gt ^; .

d) (3R, 4R) -1- benzyl-4- (3,4-dichloro-phenyl) -pyrrolidine-3-carboxylic acid Methyl ester

(3R, 4R) - (4-chloro-phenyl) -pyrrolidine-3-carboxylic acid in analogy to the synthetic procedure described in example 89 (step d) (3R, 4R) -l-Benzyl-4- (3,4-dichloro-phenyl) -pyrrolidine-3- carboxylic acid was prepared from l- Pyrrolidine-3-carboxylic acid methyl ester as a brown oil. MS m / e: 366.2 [M + H] &lt; ⁺ &gt;.

e) (3S, 4R) -1- benzyl-4- (3,4-dichloro-phenyl) -pyrrolidine-3-carboxylic acid Methyl ester

(3R, 4R) -l-benzyl-4- (4-chloro-phenyl) -pyrrolidine-3- carboxylic acid methyl ester in analogy to the synthetic procedure described in example 89 (3S, 4R) -l-benzyl-4- (3,4-dichloro-phenyl) -pyrrolidine-3-carboxylic acid methyl ester was prepared -Phenyl) -pyrrolidine-3-carboxylic acid methyl ester as a pale yellow oil. MS m / e: 366.2 [M + H] &lt; ⁺ &gt;.

f) (3S, 4R) -1- benzyl-4- (3,4-dichloro-phenyl) -pyrrolidine-3-carboxylic acid Amide

Was prepared in analogy to the synthetic procedure described in example 89 (step f) from (3S, 4R) -l-benzyl-4- (4-chloro-phenyl) -pyrrolidine- (3S, 4R) -l-benzyl-4- (3,4-dichloro-phenyl) -pyrrolidine-3-carboxylic acid methyl ester was prepared -Phenyl) -pyrrolidine-3-carboxylic acid amide as a white solid. MS m / e: 351.3 [M + H] &lt; ⁺ &gt;.

g) [(3S, 4R) -1- benzyl-4- (3,4-dichloro-phenyl) -pyrrolidin-3-yl] -carbamic acid Methyl ester

(3S, 4R) -l-benzyl-4- (4-chloro-phenyl) -pyrrolidine-3-carboxylic acid amide in analogy to the synthetic procedure described in example 89 (step g) (3S, 4R) -l-benzyl-4- (3,4-dichloro-phenyl) -pyrrolidine-3- carboxylic acid amide [ Phenyl) -pyrrolidin-3-yl] -carbamic acid methyl ester as a white solid. MS m / e: 381.3 [M + H] &lt; ⁺ &gt;.

h) (3S, 4R) -1- benzyl-4- (3,4-dichloro-phenyl) -N- methyl-pyrrolidin-3-amine

(4-chloro-phenyl) -pyrrolidin-3-yl] -carbamic acid methyl ester in analogy to the synthetic procedure described in example 89h (step h) Was prepared in accordance with the general method of example 1 from [(3S, 4R) -l-benzyl-4- (3,4-dichloro- phenyl) -pyrrolidin- Benzyl-4- (3,4-dichloro-phenyl) -pyrrolidin-3-yl] -methyl- amine as a light yellow liquid. MS m / e: 337.4 [M + H] &lt; ⁺ &gt;.

i) [(3S, 4R) -1- benzyl-4- (3,4-dichloro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-bit Lai difluoromethoxy butyl-cyclohexyl ester

Example 25 4- (trifluoromethyl) instead of 2-Cyclopropyl analogy to the synthesis procedure, ethanol described in cyclohexanol (cis / trans 1: 3) - {4 - rac using [(3S, 4R ) - 3- (3,4-dichloro-phenyl) -4-methylamino-pyrrolidine- 1-carbonyl] -piperidin- The title compound was prepared from [(3S, 4R) -l-benzyl-4- (3,4-dichloro- phenyl) -pyrrolidin- Benzyl-4- (3,4-dichloro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-trifluoromethyl-cyclohexyl ester as a white foam. MS m / e: 529.2 [M] &lt; ⁺ & gt ^; .

j) [(3S, 4R) -4- (3,4- dichloro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-trifluoromethyl-cyclohexyl ester

In analogy with the synthesis procedure described in Example 1 (step e), rac - [(3R , 4S) -1- benzyl-4- (3,4-dichloro-phenyl) -pyrrolidin-3-yl] - Methyl-carbamic acid tert-butyl ester instead of [(3S, 4R) -l-benzyl-4- (3,4- dichloro- phenyl) -pyrrolidin- The title compound was prepared from [(3S, 4R) -4- (3,4-dichloro-phenyl) -pyrrolidin-3- yl] -methyl-carbamic acid 4-trifluoromethyl- -Cyclohexyl ester as a light brown oil. MS m / e: 439.1 [M] ^&lt; ⁺ & gt ^; .

k) [(3S, 4R) -1- (5'- -cyano-3,4,5,6-tetrahydro -2H- [1,2 '] bipyridinyl-4-carbonyl) -4- ( 3,4-dichloro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-trifluoromethyl-cyclohexyl ester

The title compound was prepared in analogy to the synthetic procedure described in example 44 (step c) from 5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 ' Yl] -methyl-carbamic acid 4-fluoro-phenyl) -pyrrolidine-4-carboxylic acid was prepared from [(3S, 4R) -4- Ester instead of [(3S, 4R) -4- (3,4-dichloro-phenyl) -pyrrolidin-3- yl] -methyl-carbamic acid 4-trifluoromethyl- cyclohexyl ester, (3S, 4R) -1- (5'-Cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl-4-carbonyl) -4- -Dichloro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-trifluoromethyl-cyclohexyl ester as an off-white foam. MS m / e: 652.3 [M] ^&lt; ⁺ & gt ^; .

Example  160

{(3S, 4R) -4- (3,4- Dichloro - Phenyl ) -1- [1- (6- methyl - Pyridazine Yl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Trifluoromethyl - Cyclohexyl  Ester

n

(6-methyl-pyridazin-3-yl) -piperidine-4-carboxylic acid was used instead of 1-methylcyclopropane-l-carboxylic acid in analogy to the synthetic procedure described in example 44 To give [(3S, 4R) - (3,4-dichloro-phenyl) -pyrrolidin-3-yl] -methyl- The title compound was prepared from {(3S, 4R) -4- (3-tert-butoxycarbonylamino-phenyl) -pyrrolidin- Pyridin-3-yl) -piperidine-4-carbonyl] -pyrrolidin-3-yl} -methyl- carbamic acid 4-Trifluoromethyl-cyclohexyl ester as an off-white foam. MS m / e: 642.4 [M] ^&lt; ⁺ & gt ^; .

Example  161

[(3S, 4R) -4- (3,4- Dichloro - Phenyl )-One-( Tetrahydro -Pyran-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Trifluoromethyl - Cyclohexyl  Ester

(3S, 4R) -4- (3, 4-dihydro-4H-pyrazol-3-yl) -methanone was prepared in analogy to the synthetic procedure described in example 44 (step c) using tetrahydropyran-4-yl- (3S, 4R) -4- (3,4-Dichloro-phenyl) - pyrrolidin-3-yl] -methyl- carbamic acid 4- (3S, 4R) -4- (3,4-dichloro-phenyl) -l- (tetra (4-methyl-pyridin- Methyl-carbamic acid 4-trifluoromethyl-cyclohexyl ester as an off-white foam. MS m / e: 551.4 [M] ^&lt; ⁺ & gt ^; .

Example  162

{(3S, 4R) -4- (4- Chloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid Tetrahydro -Pyran-4-yl ester

Example 25 In analogy to the synthetic procedure described in this, by using tetrahydropyran-4-ol in place of 2-cyclopropyl ethanol rac - {4 - [(3S , 4R) -3- (3,4- dichloro- (3R, 4S) -3- ((4-methoxy-phenyl) -4-methylamino-pyrrolidine- 1- carbonyl] -piperidin- Yl] -methanone was prepared the title compound {from 4-chloro-phenyl) -4-methylamino-pyrrolidin- 1 -yl] - [1- (3S, 4R) -4- (4-Chloro-phenyl) -l- [1- (1- methyl- cyclopropanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- -Methyl-carbamic acid tetrahydro-pyran-4-yl ester as a colorless foam. MS m / e: 532.4 [M] ^&lt; ⁺ & gt ^; .

Example  163

{(3S, 4R) -4- (4- Chloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  SE-butyl ester

In analogy to the synthetic procedure described in example 25, 2-butanol was used in place of 2-cyclopropylethanol to give rac- {4 - [(3S, 4R) -3- (3,4- (3R, 4S) -3- (4-chloro-pyridin-2-ylmethyl) -piperidine-l- The title compound was prepared from {(3S, 4R (2R, 3R, 3R, 3R, 5R) Yl) -piperidin-4-carbonyl] -pyrrolidin-3-yl} -methyl-carbaldehyde Butyl ester as a colorless foam. MS m / e: 504.2 [M] ^&lt; ⁺ & gt ^; .

Example  164

{(3S, 4R) -4- (4- Chloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  2,2,2- Trifluro  Ethyl ester

(4S, 4R) -3- (3,4- dichloropyrimidin -4-yl) -ethanone using 2,2,2-trifluoroethanol instead of 2-cyclopropylethanol in analogy to the synthetic procedure described in example 25, (3R, 4S) - (1-methyl-phenyl) -4-methylamino-pyrrolidine- 1-carbonyl] -piperidin- The title compound was prepared from 3- (4-chloro-phenyl) -4-methylamino-pyrrolidin-l-yl] - [1- (1- methyl- cyclopropanecarbonyl) -piperidin- The title compound was prepared from {(3S, 4R) -4- (4-chloro-phenyl) -l- - yl} -methyl-carbamic acid 2,2,2-trifluoroethyl Ester as a colorless foam. MS m / e: 530.1 [M] &lt; ⁺ & gt ^; .

Example  165

{(3S, 4R) -4- (4- Chloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  2,2,2- Trifluro -One- methyl - ethyl ester

In analogy with the synthesis procedure described in Example 25, 1,1,1-trifluoromethyl instead of 2-cyclopropyl-ethanol and isopropanol rac - {4 - [(3S , 4R) -3- (3,4 (3R, 4S) -7-methoxy-phenyl) -4-methylamino-pyrrolidine- 1-carbonyl] -piperidin- Methyl-cyclopropanecarbonyl) -piperidin-4-yl] -methanone &lt; / RTI &gt; (4-chloro-phenyl) -l- [l- (1 -methyl- cyclopropanecarbonyl) -piperidine-4- carbonyl] -pyrrolidine- 3-yl} -methyl-carbamic acid 2,2,2-trifluoro-l-methyl-ethyl Ester as a colorless foam. S m / e: 544.2 [M] ^&lt; ⁺ & gt ^; .

Example  166

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] bipyridinyl-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  2,2,2- Trifluro -One- methyl - ethyl ester

In analogy with the synthesis procedure described in Example 25, 1,1,1-trifluoromethyl instead of 2-cyclopropyl-ethanol and isopropanol rac - {4 - [(3S , 4R) -3- (3,4 4 - [(3R, 5S) -acetylamino] -pyrrolidine-1-carbonyl] -piperidin- 1 -yl} - 4S) -3- (4-chloro-phenyl) -4-methylamino-pyrrolidine- 1-carbonyl] -3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl (5-cyano-3,4,5,6-tetrahydro-2H- [l, 2 ' , 2 '] bipyridinyl-4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 2,2,2-trifluoro-l-methyl-ethyl ester as colorless foam. MS m / e: 564.3 [M] ^&lt; ⁺ & gt ^; .

Example  167

{(3S, 4R) -4- (4- Chloro - Phenyl ) -1- [1- (4- methyl -Pyrimidin-2-yl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

(4-methyl-pyrimidin-2-yl) -piperidine-4-carboxylic acid was used instead of 1-methylcyclopropane-l-carboxylic acid in analogy to the synthetic procedure described in example 44 To give [(3S, 4R) - (3,4-dichloro-phenyl) -pyrrolidin-3-yl] -methyl- The title compound was prepared from {(3S, 4R) -4- (4-chloro-phenyl) -pyrrolidin-3-ylmethyl- 4-carbonyl] -pyrrolidin-3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester was obtained as yellow As a foam. MS m / e: 552.4 [M] ^&lt; ⁺ & gt ^; .

Example  168

[(3S, 4R) -4- (4- Chloro - Phenyl )-One-( Pyrrolidine Carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

To a stirred solution of 3 - {(3R, 4S) -3- (4-chloro-phenyl) -4 - [(4- fluoro-phenoxycarbonyl) Trifluoroacetic acid (1.64 mL, 21.4 mmol) was added to a solution of the title compound (1.17 g, 2.14 mmol) and the reaction mixture And stirred for 3 hours. This was treated with an aqueous solution of sodium carbonate (1M, 50 mL) and the organic layer was separated and washed with brine (40 mL). The aqueous layer was extracted with dichloromethane (40 mL) and the combined organic layers were dried over sodium sulfate. Concentration gave the title compound (760 mg, 79%) as a white semisolid. MS m / e: 446.1 [M + H] &lt; ⁺ &gt;.

Example  169

{(3S, 4R) -4- (4- Chloro - Phenyl ) -1- [1- (5- Fluoro -Pyrimidin-2-yl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

(5-fluoro-pyrimidin-2-yl) -piperidine-4-carboxylic acid instead of 1-methylcyclopropane-1-carboxylic acid in analogy to the synthetic procedure described in example 44 (3S, 4R) -4-tert-butoxycarbonylamino-4-fluoro-phenyl ester instead of [(3S, 4R) -4- Fluoro-phenyl ester was prepared the title compound {(3S, 4R) -4- (4-chloro-phenyl) -pyrrolidin- Yl] -piperidin-4-carbonyl] -pyrrolidin-3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester &Lt; / RTI &gt; as a yellow foam. MS m / e: 556.2 [M] ^&lt; ⁺ & gt ^; .

Example  170

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (1- Propionate - Pyrrolidine Carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

In analogy to the synthetic procedure described in example 73, rac - [(3R, 4S) -4- (3,4-dichloro-phenyl) -l- (piperidin- ) - pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester was used in the place of [(3S, 4R) -4- Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester was prepared the title compound [(3S, 4R) -4- Yl-pyrrolidine-3-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester as a pale yellow oil. MS m / e: 502.2 [M + H] &lt; ⁺ &gt;.

Example  171

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (1-cyclopropanecarbonyl- Pyrrolidine -3-carbonyl) - &lt; / RTI &gt; Loridine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

Example 73 In analogy to the synthetic procedure described in, using cyclopropane carbonyl chloride instead of propionyl chloride, rac - [-4- (3,4- dichloro-phenyl) (3R, 4S) -1- (P 4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester instead of [ (3S, 4R) -4- (4-chloro-phenyl) -pyrrolidin-3-yl] -methyl- Pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester as colorless oil. MS m / e: 514.4 [M] ^&lt; ⁺ & gt ^; .

Example  172

{(3S, 4R) -4- (4- Chloro - Phenyl ) -1- [1- (2- Methoxy -Acetyl) - Pyrrolidine -3-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

Example 73 In analogy to the synthetic procedure described in, using methoxyacetyl chloride instead of propionyl chloride, rac - [(3R, 4S) -4- (3,4- dichloro-phenyl) -1- (piperidin 4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester instead of [(3S, (3S, 4R) -4- (4-chloro-phenyl) - pyrrolidine-3-carbonyl) -pyrrolidin- 3-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester as a pale yellow oil Respectively. MS m / e: 518.3 [M + H] &lt; ⁺ &gt;.

Example  173

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] bipyridinyl-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid Cyclobutyl  Ester

Example 25 In analogy to the synthetic procedure described in this, by using the cycloalkyl-butanol instead of 2-cyclopropyl ethanol rac - {4 - [(3S , 4R) -3- (3,4- dichloro-phenyl) -4- 4 - [(3R, 4S) -3- (4-chloro-pyridin-2-ylmethyl) -piperidine-l- - phenyl) -4-methylamino-pyrrolidine-l-carbonyl] -3,4,5,6-tetrahydro-2H- [ [(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid cyclobutyl ester as colorless foam. MS m / e: 522.4 [M] ^&lt; ⁺ & gt ^; .

Example  174

{(3S, 4R) -4- (4- Chloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid Cyclobutyl  Ester

Example 25 In analogy to the synthetic procedure described in this, by using the cycloalkyl-butanol instead of 2-cyclopropyl ethanol rac - {4 - [(3S , 4R) -3- (3,4- dichloro-phenyl) -4- (3R, 4S) -3- (4-chloro-phenyl) -piperidine-l-carbonyl] -piperidin- 1 -yl} - The title compound was prepared from {(3S, 4R) -lH-indol-3-yl) -methylamino-pyrrolidin- -Piperidin-4-carbonyl] -pyrrolidin-3-yl} -methyl-carbamic acid ethyl ester was prepared from 4- (4-chloro-phenyl) Cyclobutyl Ester as a colorless foam. MS m / e: 502.3 [M] ^&lt; ⁺ & gt ^; .

Example  175

{(3S, 4R) -4- (4- Chloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  2,2,3,3- Tetrafluorocyclobutyl  Ester

In analogy to the synthetic procedure described in example 25, by using 2,2,3,3-tetrafluorocyclobutanol instead of 2-cyclopropylethanol, rac - {4 - [(3S, 4R) -3- Instead of [(3R, 4S) -2-methyl-pyrrolidine-1-carbonyl] -piperidin- 4-yl] - (1-methyl-cyclopropanecarbonyl) -piperidin-4-yl] - Methanone was prepared the title compound {(3S, 4R) -4- (4-chloro-phenyl) -1- [1- (1- methyl- cyclopropanecarbonyl) -piperidine- Pyridin-3-yl} -methyl-carbamic acid 2,2,3,3-tetrafluorocyclobutyl ester as colorless foam. MS m / e: 574.5 [M] ^&lt; ⁺ & gt ^; .

Example  176

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] bipyridinyl-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  2,2,3,3- Tetrafluorocyclobutyl  Ester

In analogy to the synthetic procedure described in example 25, by using 2,2,3,3-tetrafluorocyclobutanol instead of 2-cyclopropylethanol, rac - {4 - [(3S, 4R) -3- (4-chloro-phenyl) -4-methylamino-pyrrolidine- 1-carbonyl] -piperidin- 1 -yl} - 3R, 4S) -3- (4-chloro-phenyl) -4-methylamino-pyrrolidine- 1-carbonyl] -3,4,5,6-tetrahydro-2H- [ (3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H-pyridin- [1,2 '] bipyridinyl-4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 2,2,3,3-tetrafluorocyclobutyl ester as colorless foam. MS m / e: 594.4 [M] ^&lt; ⁺ & gt ^; .

Example  177

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] bipyridinyl-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  3,3,3- Trifluro -One- methyl -Profile ester

Using 4,4,4-trifluorobutan-2-ol instead of 2-cyclopropylethanol, rac - {4 - [(3S, 4R) -3- ( Methyl-cyclopropyl) -methanone was prepared in analogy to the procedure described for the synthesis of 4- [2- (4-chloro-phenyl) -4-methylamino-pyrrolidine- (3R, 4S) -3- (4-chloro-phenyl) -4-methylamino-pyrrolidine- 1- carbonyl] -3,4,5,6-tetrahydro- (5-cyano-3,4,5,6-tetrahydro-2H- - [1,2 '] bipyridinyl-4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 3,3,3- trifluoro-l- methyl- propyl ester as a colorless foam . MS m / e: 578.4 [M] ^&lt; ⁺ & gt ^; .

Example  178

{(3S, 4R) -4- (4- Chloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  3,3,3- Trifluro -One- methyl -Profile ester

Using 4,4,4-trifluorobutan-2-ol instead of 2-cyclopropylethanol, rac - {4 - [(3S, 4R) -3- ( Instead of [(3R) -lH-pyrrolo [2,3-c] pyridin- (4-chloro-phenyl) -4-methylamino-pyrrolidin- 1 -yl] -Methanone was prepared the title compound {(3S, 4R) -4- (4-chloro-phenyl) -l- 3-yl} -methyl-carbamic acid 3,3,3-trifluoro-l-methyl-propyl ester as colorless foam. MS m / e: 558.4 [M] ^&lt; ⁺ & gt ^; .

Example  179

{(3S, 4R) -4- (4- Chloro - Phenyl ) -1- [1- ( Tetrahydro -Pyran-4-yl) - Pyrrolidine -3-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

(3S, 4R) -4- (4-chloro-phenyl) -l- (pyrrolidine-3-carbonyl) -pyrrolidin- Tetrahydro-4H-pyran-4-one (25 mg, 0.25 mmol) was added to a solution of 4-fluoro-phenyl ester (408 mg, 0.92 mmol). After stirring at ambient temperature for 15 minutes sodium triacetoxyborohydride (252 mg, 1.19 mmol) was added and stirring continued at ambient temperature for 4 hours. The reaction mixture was diluted with ethyl acetate (10 mL) and washed with an aqueous solution of sodium carbonate (10 mL). The aqueous layer was extracted with ethyl acetate (10 mL) and the combined organic layers were dried over sodium sulfate. Concentrated, and purified by chromatography to give the (SiO _2, ethyl acetate: 0 to 80: 20: methanol = 100) to give the title compound (115 mg, 24%), open as a yellow oil. MS m / e: 530.3 [M] ^&lt; ⁺ & gt ^; .

Example  180

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Methane sulfonyl -3,4,5,6- Tetrahydro -2H- [1,2 '] &lt; / RTI & Epiri 4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

To a solution of 20 mg (0.043 mmol) of [(3S, 4R) -4- (4-chloro-phenyl) - 1- (piperidine- 4- 4- carbonyl) -pyrrolidin- A mixture of 11.2 μL (0.065 mmol) of DIPEA and 12.8 mg (0.054 mmol) of 2-bromo-5- (methylsulfonyl) pyridine was heated to 60 ° C. overnight . The mixture was purified by preparative HPLC on reversed phase eluting with a gradient formed from acetonitrile, water and NEt ₃ to give the title compound as a pale yellow viscous oil after evaporation of the product containing fractions. MS m / e: 615.3 [M] ^&lt; ⁺ & gt ^; .

Example  181

 [(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Trifluoromethyl -3,4,5,6- Tetrahydro -2H- [1,2 '] Bipyridinyl Carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

[(3S, 4R) -4- (4-Chloro-phenyl) -1- (5'-methanesulfonyl-3,4,5,6-tetrahydro- 4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester (Example 180) 3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester and 2-bromo- (trifluoromethyl) -piperidine- ) Pyridine (commercially available) as a pale yellow viscous oil. MS m / e: 605.4 [M] ^&lt; ⁺ & gt ^; .

Example  182

 [(3S, 4R) -1- (5'-Acetyl-3,4,5,6- Tetrahydro -2H- [1,2 '] Bipyridinyl -4-carbonyl) -4- (4- Chloro - Phenyl ) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

[(3S, 4R) -4- (4-Chloro-phenyl) -1- (5'-methanesulfonyl-3,4,5,6-tetrahydro- 4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester (Example 180) 3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester and 2-bromo- (trifluoromethyl) -piperidine- ) Pyridine (commercially available) as a pale yellow viscous oil. MS m / e: 579.4 [M] ^&lt; ⁺ & gt ^; .

Example  183

 [(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (1-pyrimidin-2-yl-piperidine-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

[(3S, 4R) -4- (4-Chloro-phenyl) -1- (5'-methanesulfonyl-3,4,5,6-tetrahydro- 4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester (Example 180) -Methyl-carbamic acid 4-fluoro-phenyl ester and 2-bromo-pyrimidine (commercially available as &lt; RTI ID = 0.0 &&Lt; / RTI &gt; available) as the pale yellow viscous oil. MS m / e: 538.4 [M] ^&lt; ⁺ & gt ^; .

Example  184

 {(3S, 4R) -4- (4- Chloro - Phenyl ) -1- [1- (5- Chloro -Pyrimidin-2-yl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

[(3S, 4R) -4- (4-Chloro-phenyl) -1- (5'-methanesulfonyl-3,4,5,6-tetrahydro- 4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester (Example 180) 3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester and 3,6-dichloropyrimidine (commercially available (commercially available) &Lt; / RTI &gt; as the title compound as a pale yellow viscous oil. MS m / e: 572.2 [M] ^&lt; ⁺ & gt ^; .

Example  185

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (4'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] bipyridinyl-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

[(3S, 4R) -4- (4-Chloro-phenyl) -1- (5'-methanesulfonyl-3,4,5,6-tetrahydro- 4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester (Example 180) (2-chloro-phenyl) - l- (piperidine-4-carbonyl) -pyrrolidin- Commercially available) of the title compound as a pale yellow viscous oil. MS m / e: 562.4 [M] ^&lt; ⁺ & gt ^; .

Example  186

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (3 ' - Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] &lt; / RTI & Epithe 4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

[(3S, 4R) -4- (4-Chloro-phenyl) -1- (5'-methanesulfonyl-3,4,5,6-tetrahydro- 4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester (Example 180) -Pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester and 2-chloronicotinonitrile (commercially available The title compound was obtained as a pale yellow viscous oil. MS m / e: 562.3 [M] ^&lt; ⁺ & gt ^; .

Example  187

 {(3S, 4R) -4- (4- Chloro - Phenyl ) -1- [1- (6- Cyano - pyrazin-2-yl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

[(3S, 4R) -4- (4-Chloro-phenyl) -1- (5'-methanesulfonyl-3,4,5,6-tetrahydro- 4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester (Example 180) Yl] -methyl-carbamic acid 4-fluoro-phenyl ester and 6-cyano-2-chloropyrazine (prepared from Commercially available) of the title compound as a pale yellow viscous oil. MS m / e: 563.3 [M] ^&lt; ⁺ & gt ^; .

Example  188

 [(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (3 ' - Chloro -5'- Trifluoromethyl -3,4,5,6-tetrahydro-2H- [l, 2 ' Bipyridinyl Carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  4-fluoro- Phenyl  Ester

[(3S, 4R) -4- (4-Chloro-phenyl) -1- (5'-methanesulfonyl-3,4,5,6-tetrahydro- 4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester (Example 180) 3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester and 2,3, -dichloro-5- (4-fluoro-phenyl) (Trifluoromethyl) pyridine (commercially available) as a pale yellow viscous oil. MS m / e: 639.3 [M] ^&lt; ⁺ & gt ^; .

Example  189

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (6'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] bipyridinyl-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

[(3S, 4R) -4- (4-Chloro-phenyl) -1- (5'-methanesulfonyl-3,4,5,6-tetrahydro- 4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester (Example 180) 3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester and 2-chloro-6-cyanopyridine (prepared from Commercially available) of the title compound as a pale yellow viscous oil. MS m / e: 562.3 [M] ^&lt; ⁺ & gt ^; .

Example  190

 {(3S, 4R) -4- (4- Chloro - Phenyl ) -1- [1- (5- Methoxy -Pyrimidin-2-yl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

[(3S, 4R) -4- (4-Chloro-phenyl) -1- (5'-methanesulfonyl-3,4,5,6-tetrahydro- 4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester (Example 180) 3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester and 2-chloro-5-methoxy-pyrimidine Lt; / RTI &gt; (commercially available) as the light brown viscous oil. MS m / e: 568.4 [M] ^&lt; ⁺ & gt ^; .

Example  191

 [(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (1-Pyrimidin-4-yl-piperidine-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

[(3S, 4R) -4- (4-Chloro-phenyl) -1- (5'-methanesulfonyl-3,4,5,6-tetrahydro- 4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester (Example 180) Fluoro-phenyl ester and 2-chloro-pyrimidine (commercially available as &lt; RTI ID = 0.0 &gt; The title compound was obtained as a pale yellow viscous oil. MS m / e: 538.4 [M] ^&lt; ⁺ & gt ^; .

Example  192

 {(3S, 4R) -4- (4- Chloro - Phenyl ) -1- [1- (5- Cyano -Pyrimidin-2-yl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

[(3S, 4R) -4- (4-Chloro-phenyl) -1- (5'-methanesulfonyl-3,4,5,6-tetrahydro- 4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester (Example 180) -Pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester and 2-chloropyrimidine-5-carbonitrile (Commercially available) of the title compound as a pale yellow waxy solid. MS m / e: 563.4 [M] ^&lt; ⁺ & gt ^; .

Example  193

 {(3S, 4R) -4- (4- Chloro - Phenyl ) -1- [1- (5- Cyano - pyrazin-2-yl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

[(3S, 4R) -4- (4-Chloro-phenyl) -1- (5'-methanesulfonyl-3,4,5,6-tetrahydro- 4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester (Example 180) -Pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester and 5-bromopyrazine-2-carbonitrile (Commercially available) of the title compound as a pale yellow viscous oil. MS m / e: 563.3 [M] ^&lt; ⁺ & gt ^; .

Example  194

 [(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- methyl -3,4,5,6- Tetrahydro -2H- [1,2 '] bipyridinyl-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

To a solution of 26.7 mg (0.085 mmol) of [(3S, 4R) -4- (4-chloro-phenyl) -pyrrolidin-3- yl] -methyl- carbamic acid 4- fluoro-phenyl ester, 15 (commercially available), 31 mg (0.082 mmol) of HATU and 70 [mu] l (0.409 mmol) of DIPEA were added to a solution of 1- (5-methyl-2-pyridinel) -4-piperidinecarboxylic acid The mixture was shaken at room temperature for 1 hour. The mixture was purified by preparative HPLC on reversed phase eluting with a gradient formed from acetonitrile, water and NEt ₃ to give the title compound as an off-white solid after evaporation of the product containing fractions. MS m / e: 551.4 [M] ^&lt; ⁺ & gt ^; .

Example  195

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Fluoro -3,4,5,6- Tetrahydro -2H- [1,2 '] &lt; / RTI & Epiri 4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

a) 5'- Fluoro -3,4,5,6- Tetrahydro -2H- [1,2 '] Bipyridinyl -4- Carboxylic acid  Ethyl ester

A mixture of 3.4 g (20 mmol) 2-bromo-5-fluoropyridine, 4.61 g (29 mmol) ethyl isonipecotate and 3.79 g (29 mmol) DIPEA in 5 mL NMP was treated with 170 RTI ID = 0.0 &gt; 200 C &lt; / RTI &gt; for 60 minutes. After cooling to room temperature, water was added and the mixture was extracted with ethyl acetate and heptane. The combined organic layers are washed with brine, dried over Na ₂ SO ₄ sulphate, filtered, and evaporated to dryness. The residue was purified by column chromatography on silica eluting with a gradient from heptane and ethyl acetate. The product containing fractions were evaporated to give 1.5 g (30%) of the title compound as a pale yellow oil. MS m / e: 253.3 [M] ^&lt; ⁺ & gt ^; .

b) 5'- Fluoro -3,4,5,6- Tetrahydro -2H- [1,2 '] Bipyridinyl -4- Carboxylic acid

To a solution of 4 g (16 mmol) of 5'-fluoro-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- a mixture of carboxylic acid ethyl ester and 0.832 g (20 mmol) of LiOH and H ₂ O was stirred for 2 h at 20 ℃. Acetic acid, water and ethyl acetate were added until a pH of 6 was reached. The mixture was extracted with ethyl acetate and wash the combined organic layers with brine, dried, filtered with Na ₂ SO ₄ and evaporated to dryness. The residue was purified by column chromatography on silica eluting with a gradient from heptane and ethyl acetate. The product containing fractions were evaporated to yield 3.1 g (87%) of the title compound as off-white solid. MS m / e: 223.1 [MH] &lt; + &gt;.

c) [(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Fluoro -3,4,5,6- Tetrahydro -2H- [1,2 '] &lt; / RTI & Epiri 4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

[(3S, 4R) -4- (4-chloro-phenyl) -l- (5'-methyl-3,4,5,6-tetrahydro- Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester (example 194) - phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester and 5'-fluoro-3,4,5,6-tetrahydro-2H- [ 4-carboxylic &lt; / RTI &gt; acid, the title compound was obtained as an off-white solid. MS m / e: 555.2 [M] ^&lt; ⁺ & gt ^; .

Example  196

[(3S, 4R) -1- (5 ' - Carbamoyl -3,4,5,6- Tetrahydro -2H- [1,2 '] Bipyridinyl -4-carbonyl) -4- (4- Chloro - Phenyl ) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

[(3S, 4R) -4- (4-chloro-phenyl) -l- (5'-methyl-3,4,5,6-tetrahydro- Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester (example 194) - phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester and 5'-carbamoyl-3,4,5,6-tetrahydro-2H- [ 4-carboxylic acid, the title compound was obtained as a light brown viscous oil. MS m / e: 580.4 [M] ^&lt; ⁺ & gt ^; .

Example  197

{(3S, 4R) -4- (4- Chloro - Phenyl ) -1- [1- (6- Methoxy - Pyridazine Yl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

a) 1- (6- Methoxy - Pyridazine 3-yl) -piperidin-4- Carboxylic acid  Ethyl ester

A solution of 4.33 g (30 mmol) 3-chloro-6-methoxypyridazine, 5.66 g (36 mmol) ethyl isonipecotate, 3.46 g (36 mmol) sodium tert-butylate in 60 mL toluene, 0.56 g (0.9 mmol) of BINAP and 0.55 g (0.5 mmol) of Pd ₂ dba ₃ was heated to 100 &lt; 0 &gt; C for 90 min. After cooling to room temperature, water was added and the mixture was extracted with ethyl acetate. The combined organic layers are washed with brine, dried over Na ₂ SO ₄ sulphate, filtered, and evaporated to dryness. The residue was purified by column chromatography on silica eluting with a gradient from heptane and ethyl acetate. The product containing fractions were evaporated to yield 3.2 g (34%) of the title compound as an orange solid. MS m / e: 266.3 [M + H] &lt; ⁺ &gt;.

b) 1- (6- Methoxy - Pyridazine 3-yl) -piperidin-4- Carboxylic acid

Similar to the procedure for the synthesis of 5'-fluoro-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl-4-carboxylic acid, 1- (6-methoxy- 3-yl) -piperidine-4-carboxylic acid ethyl ester was saponified with LiOH.H ₂ O to give the title compound. The title compound was isolated as an orange solid. MS m / e: 236.2 [MH] &lt; + &gt;.

c) {(3S, 4R) -4- (4- Chloro - Phenyl ) -1- [1- (6- Methoxy - Pyridazine Yl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

[(3S, 4R) -4- (4-chloro-phenyl) -l- (5'-methyl-3,4,5,6-tetrahydro- Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester (example 194) -Phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester and 1- (6-methoxy-pyridazin- The compound was obtained as a pale yellow viscous oil. MS m / e: 568.5 [M + H] &lt; ⁺ &gt;.

Example  198

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (6'- Cyano -3,4,5,6- Tetrahydro -2H- [1,3 '] bipyridinyl-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

a) 6'- Cyano -3,4,5,6- Tetrahydro -2H- [1,3 '] Bipyridinyl -4- Carboxylic acid  Ethyl ester

Similarly to the procedure for the synthesis of 1- (6-methoxy-pyridazin-3-yl) -piperidine-4-carboxylic acid ethyl ester, the title compound from 5-bromo-cyanopyridine and ethyl isonipecotate As a viscous yellow oil. MS m / e: 260.3 [M + H] &lt; ⁺ &gt;.

b) 6'- Cyano -3,4,5,6- Tetrahydro -2H- [1,3 '] Bipyridinyl -4- Carboxylic acid

Similar to the procedure for the synthesis of 5'-fluoro-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl-4-carboxylic acid, 6'-cyano- 5,6-tetrahydro-2H- [1,3 '] bipyridinyl-4-carboxylic acid ethyl ester was saponified with LiOH.H ₂ O to give the title compound. The title compound was isolated as a yellow solid. MS m / e: 230 [MH] &lt; + &gt;.

c) [(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (6'- Cyano -3,4,5,6- Tetrahydro -2H- [1,3 '] &lt; / RTI & Epiri 4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

[(3S, 4R) -4- (4-chloro-phenyl) -l- (5'-methyl-3,4,5,6-tetrahydro- Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester (example 194) - phenyl] -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester and 6'-cyano-3,4,5,6-tetrahydro-2H- [ Carboxylic &lt; / RTI &gt; acid as the pale yellow viscous oil. MS m / e: 562.3 [M + H] &lt; ⁺ &gt;.

Example  199

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Chloro -3,4,5,6- Tetrahydro -2H- [1,2 '] bipyridinyl-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

[(3S, 4R) -4- (4-chloro-phenyl) -l- (5'-methyl-3,4,5,6-tetrahydro- Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester (example 194) -Phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester and 5'-chloro-3,4,5,6-tetrahydro-2H- [ Pyridine-4-carboxylic acid, the title compound was obtained as a pale yellow viscous oil. MS m / e: 571.3 [M + H] &lt; ⁺ &gt;.

Example  200

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] bipyridinyl-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid Phenyl  Ester

To a solution of 25 mg (0.059 mmol) 4 - [(3R, 4S) -3- (4-chloro-phenyl) -4-methylamino-pyrrolidine- 1-carbonyl] A mixture of 11.5 mg (0.074 mmol) of phenyl chloroformate and 11.4 mg (0.088 mmol) of DIPEA was added at 5 &lt; 0 &gt; C to a stirred solution of 6-tetrahydro-2H- [1,2 '] bipyridinyl-5'-carbonitrile, Stir for 15 min and at room temperature overnight. Adding ESOL root, and the mixture was evaporated to dryness, and the residue was purified by DCM, methanol, and purified by column chromatography on silica eluting with a gradient formed from NH _3. The product containing fractions were evaporated to yield 27 mg (84%) of the title compound as pale yellow viscous oil. MS m / e: 544.4 [M + H] &lt; ⁺ &gt;.

Example  201

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] bipyridinyl-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Methoxy - Phenyl  Ester

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- 4-yl) -carbamoyl] -pyrrolidin-3-yl] -methyl-carbamic acid phenyl ester was prepared 4 - [(3R, Carbonyl] -3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl-5'-carbonitrile and 4-methoxyphenyl chloroform The compound was obtained as a pale yellow viscous oil. MS m / e: 574.5 [M + H] &lt; ⁺ &gt;.

Example  202

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] bipyridinyl-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  p- Tolyl  Ester

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- 4-yl) -carbamoyl] -pyrrolidin-3-yl] -methyl-carbamic acid phenyl ester was prepared 4 - [(3R, Carbonyl] -3,4,5,6-tetrahydro-2H- [l, 2 &apos;] bipyridinyl-5 ' -carbonitrile and p- Obtained as a pale yellow viscous oil. MS m / e: 558.4 [M + H] &lt; ⁺ &gt;.

Example  203

[(3S, 4R) -4- (4 -chloro - phenyl ) -1- (5'- cyano- 3,4,5,6- tetrahydro- 2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin- 3 - yl] -methyl - carbamic acid 4 -chloro - phenyl ester

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- 4-yl) -carbamoyl] -pyrrolidin-3-yl] -methyl-carbamic acid phenyl ester was prepared 4 - [(3R, Carbonyl] -3,4,5,6-tetrahydro-2H- [l, 2 &apos;] bipyridinyl-5 ' -carbonitrile and 4- As a pale yellow viscous oil. MS m / e: 578.4 [M + H] &lt; ⁺ &gt;.

Example  204

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] bipyridinyl-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid Cyclopentyl  Ester

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- 4-yl) -carbamoyl] -pyrrolidin-3-yl] -methyl-carbamic acid phenyl ester was prepared 4 - [(3R, Carbonyl] -3,4,5,6-tetrahydro-2H- [l, 2 &apos;] bipyridinyl-5 ' -carbonitrile and cyclopentyl chloroform, As a viscous oil. MS m / e: 536.3 [M + H] &lt; ⁺ &gt;.

Example  205

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] bipyridinyl-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  2,2- Dimethyl -Profile ester

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- 4-yl) -carbamoyl] -pyrrolidin-3-yl] -methyl-carbamic acid phenyl ester was prepared 4 - [(3R, Carbonyl] -3,4,5,6-tetrahydro-2H- [1,2 &apos;] bipyridinyl-5 ' -carbonitrile and neopentyl chloroform, As a viscous oil. MS m / e: 538.4 [M + H] &lt; ⁺ &gt;.

Example  206

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] bipyridinyl-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  2- Methoxy - ethyl ester

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- 4-yl) -carbamoyl] -pyrrolidin-3-yl] -methyl-carbamic acid phenyl ester was prepared 4 - [(3R, Carbonyl] -3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl-5'-carbonitrile and chloroformic acid 2-methoxyethyl ester was prepared The title compound was obtained as a colorless viscous oil. MS m / e: 526.4 [M + H] &lt; ⁺ &gt;.

Example  207

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] bipyridinyl-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Trifluoromethyl - Phenyl  Ester

A solution of 243 mg (1.5 mmol) of 4-hydroxybenzotrifluoride in 3 mL of THF at -70 &lt; 0 &gt; C was treated with 1 mL (1.6 mmol) of nBuLi (1.6 M in hexane) Respectively. 156 mg (0.526 mmol) of triphosgene in 3 mL of THF was slowly added and warmed to room temperature. This mixture was added to a solution of 60 mg (0.142 mmol) of 4 - [(3R, 4S) -3- (4-chloro-phenyl) -4- methylamino-pyrrolidine- -3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl-5'-carbonitrile and 22.8 mg (0.177 mmol) of DIPEA and stirred for 15 minutes. Isolute was added and the mixture was evaporated to dryness and the residue was subjected to column chromatography on silica eluting with a gradient formed from DCM, methanol and NH ₃ and then purified by preparative HPLC on reversed phase. Evaporation of the product containing fractions gave 30 mg (35%) of the title compound as a pale yellow viscous oil. MS m / e: 612.3 [M + H] &lt; ⁺ &gt;.

Example  208

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] bipyridinyl-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  2,4- Difluoro - Phenyl s foundation

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- (3R, 4S) -3, 4-dihydro-2H-pyridin-2-ylmethoxy) - carbonyl) -pyrrolidin- - (4-chloro-phenyl) -4-methylamino-pyrrolidine- 1-carbonyl] -3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- Carbonitrile and 2,4-difluorophenol, the title compound was obtained as a pale yellow viscous oil. MS m / e: 580.4 [M + H] &lt; ⁺ &gt;.

Example  209

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] bipyridinyl-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  3,4- Difluoro - Phenyl s foundation

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- (3R, 4S) -3, 4-dihydro-2H-pyridin-2-ylmethoxy) - carbonyl) -pyrrolidin- - (4-chloro-phenyl) -4-methylamino-pyrrolidine- 1-carbonyl] -3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- Carbonitrile and 3,4-difluorophenol, the title compound was obtained as a pale yellow viscous oil. MS m / e: 580.3 [M + H] &lt; ⁺ &gt;.

Example  210

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (6'- Cyano -3,4,5,6- Tetrahydro -2H- [1,3 '] bipyridinyl-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  3,5- Difluoro - Phenyl s foundation

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- (3R, 4S) -3, 4-dihydro-2H-pyridin-2-ylmethoxy) - carbonyl) -pyrrolidin- - (4-chloro-phenyl) -4-methylamino-pyrrolidine- 1-carbonyl] -3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- Carbonitrile and 3,5-difluorophenol, the title compound was obtained as colorless viscous oil. MS m / e: 580.3 [M + H] &lt; ⁺ &gt;.

Example  211

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] bipyridinyl-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  2,3- Difluoro - Phenyl s foundation

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- (3R, 4S) -3, 4-dihydro-2H-pyridin-2-ylmethoxy) - carbonyl) -pyrrolidin- - (4-chloro-phenyl) -4-methylamino-pyrrolidine- 1-carbonyl] -3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- Carbonitrile and 2,4-difluorophenol, the title compound was obtained as colorless viscous oil. MS m / e: 580.4 [M + H] &lt; ⁺ &gt;.

Example  212

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] bipyridinyl-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  2- Fluoro - Phenyl  Ester

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- (3R, 4S) -3, 4-dihydro-2H-pyridin-2-ylmethoxy) - carbonyl) -pyrrolidin- - (4-chloro-phenyl) -4-methylamino-pyrrolidine- 1-carbonyl] -3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- Carbonitrile and 2-fluorophenol, the title compound was obtained as colorless viscous oil. MS m / e: 562.3 [M + H] &lt; ⁺ &gt;.

Example  213

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] bipyridinyl-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  2- Chloro - Phenyl  Ester

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- (3R, 4S) -3, 4-dihydro-2H-pyridin-2-ylmethoxy) - carbonyl) -pyrrolidin- - (4-chloro-phenyl) -4-methylamino-pyrrolidine- 1-carbonyl] -3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- Carbonitrile and 2-chlorophenol, the title compound was obtained as colorless viscous oil. MS m / e: 578.3 [M + H] &lt; ⁺ &gt;.

Example  214

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] bipyridinyl-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  3- Fluoro -Profile ester

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- (3R, 4S) -3, 4-dihydro-2H-pyridin-2-ylmethoxy) - carbonyl) -pyrrolidin- - (4-chloro-phenyl) -4-methylamino-pyrrolidine- 1-carbonyl] -3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- Carbonitrile and 3-fluoropropane-1-ol, the title compound was obtained as colorless viscous oil. MS m / e: 528.3 [M + H] &lt; ⁺ &gt;.

Example  215

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] bipyridinyl-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid Cyclopropylmethyl  Ester

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- (3R, 4S) -3, 4-dihydro-2H-pyridin-2-ylmethoxy) - carbonyl) -pyrrolidin- - (4-chloro-phenyl) -4-methylamino-pyrrolidine- 1-carbonyl] -3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- The title compound was obtained as pale yellow viscous oil from carbonitrile and cyclopropyl-methanol. MS m / e: 522.4 [M + H] &lt; ⁺ &gt;.

Example  216

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] &lt; / RTI & Epithe 4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  3- Methoxy -Profile ester

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- (3R, 4S) -3, 4-dihydro-2H-pyridin-2-ylmethoxy) - carbonyl) -pyrrolidin- - (4-chloro-phenyl) -4-methylamino-pyrrolidine- 1-carbonyl] -3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- Carbonnitrile and 3-methoxy-propan-l-ol, the title compound was obtained as a colorless yellow viscous oil. MS m / e: 540.4 [M + H] &lt; ⁺ &gt;.

Example  217

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] bipyridinyl-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  One- methyl - Cyclopropylmethyl  Ester

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- (3R, 4S) -3, 4-dihydro-2H-pyridin-2-ylmethoxy) - carbonyl) -pyrrolidin- - (4-chloro-phenyl) -4-methylamino-pyrrolidine- 1-carbonyl] -3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- Carbonitrile and (1-methyl-cyclopropyl) -methanol as the colorless yellow viscous oil. MS m / e: 536.4 [M + H] &lt; ⁺ &gt;.

Example  218

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] bipyridinyl-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  3- methyl - Oxetane -3- Yl methyl s foundation

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- (3R, 4S) -3, 4-dihydro-2H-pyridin-2-ylmethoxy) - carbonyl) -pyrrolidin- - (4-chloro-phenyl) -4-methylamino-pyrrolidine- 1-carbonyl] -3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- Carbonitrile and (3-methyl-oxetan-3-yl) -methanol as the colorless yellow viscous oil. MS m / e: 552.5 [M + H] &lt; ⁺ &gt;.

Example  219

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] bipyridinyl-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  2- Cyclopropyl -ethyl s foundation

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- (3R, 4S) -3, 4-dihydro-2H-pyridin-2-ylmethoxy) - carbonyl) -pyrrolidin- - (4-chloro-phenyl) -4-methylamino-pyrrolidine- 1-carbonyl] -3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- Carbonitrile and 2-cyclopropyl-ethanol, the title compound was obtained as colorless viscous oil. MS m / e: 536.4 [M + H] &lt; ⁺ &gt;.

Example  220

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] &lt; / RTI & Epithe 4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- methyl - Cyclohexyl  Ester

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- (3R, 4S) -3, 4-dihydro-2H-pyridin-2-ylmethoxy) - carbonyl) -pyrrolidin- - (4-chloro-phenyl) -4-methylamino-pyrrolidine- 1-carbonyl] -3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- Carbonitrile and 4-methylcyclohexanol, the title compound was obtained as colorless viscous oil. MS m / e: 564.5 [M + H] &lt; ⁺ &gt;.

Example  221

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] bipyridinyl-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- methyl - Cyclohexyl  Ester

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- (3R, 4S) -3, 4-dihydro-2H-pyridin-2-ylmethoxy) - carbonyl) -pyrrolidin- - (4-chloro-phenyl) -4-methylamino-pyrrolidine- 1-carbonyl] -3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- Carbonitrile and 4-methylcyclohexanol, the title compound was obtained as colorless viscous oil. MS m / e: 564.4 [M + H] &lt; ⁺ &gt;.

Example  222

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] bipyridinyl-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  2- Methoxy -One- methyl - ethyl ester

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- (3R, 4S) -3, 4-dihydro-2H-pyridin-2-ylmethoxy) - carbonyl) -pyrrolidin- - (4-chloro-phenyl) -4-methylamino-pyrrolidine- 1-carbonyl] -3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- Carbonnitrile and 1-methoxy-propan-2-ol, the title compound was obtained as colorless viscous oil. MS m / e: 540.4 [M + H] &lt; ⁺ &gt;.

Example  223

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] bipyridinyl-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  2- Fluoro - ethyl ester

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- (3R, 4S) -3, 4-dihydro-2H-pyridin-2-ylmethoxy) - carbonyl) -pyrrolidin- - (4-chloro-phenyl) -4-methylamino-pyrrolidine- 1-carbonyl] -3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- Carbonitrile and 2-fluoro-ethanol, the title compound was obtained as yellow viscous oil. MS m / e: 514.4 [M + H] &lt; ⁺ &gt;.

Example  224

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] bipyridinyl-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Methane sulfonyl - Phenyl  Ester

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- (3R, 4S) -3, 4-dihydro-2H-pyridin-2-ylmethoxy) - carbonyl) -pyrrolidin- - (4-chloro-phenyl) -4-methylamino-pyrrolidine- 1-carbonyl] -3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- Carbonitrile and 4-methanesulfonyl-phenol, the title compound was obtained as yellow viscous oil. MS m / e: 622.4 [M + H] &lt; ⁺ &gt;.

Example  225

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] bipyridinyl-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  3- Cyano - Phenyl  Ester

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- (3R, 4S) -3, 4-dihydro-2H-pyridin-2-ylmethoxy) - carbonyl) -pyrrolidin- - (4-chloro-phenyl) -4-methylamino-pyrrolidine- 1-carbonyl] -3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- Carbonitrile and 3-hydroxy-benzonitrile, the title compound was obtained as colorless viscous oil. MS m / e: 569.4 [M + H] &lt; ⁺ &gt;.

Example  226

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] bipyridinyl-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  1- (4- Fluoro - Phenyl ) - Ethyl The

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- (3R, 4S) -3, 4-dihydro-2H-pyridin-2-ylmethoxy) - carbonyl) -pyrrolidin- - (4-chloro-phenyl) -4-methylamino-pyrrolidine- 1-carbonyl] -3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- The title compound was obtained as colorless viscous oil from carbonitrile and 1- (4-fluoro-phenyl) -ethanol. MS m / e: 590.4 [M + H] &lt; ⁺ &gt;.

Example  227

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] bipyridinyl-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  2- Fluoro -One- Fluoromethyl - ethyl ester

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- (3R, 4S) -3, 4-dihydro-2H-pyridin-2-ylmethoxy) - carbonyl) -pyrrolidin- - (4-chloro-phenyl) -4-methylamino-pyrrolidine- 1-carbonyl] -3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- Carbonitrile and 1,3-difluoro-propan-2-ol, the title compound was obtained as colorless viscous oil. MS m / e: 546.3 [M + H] &lt; ⁺ &gt;.

Example  228

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] bipyridinyl-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Cyano - Phenyl  Ester

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- (3R, 4S) -3, 4-dihydro-2H-pyridin-2-ylmethoxy) - carbonyl) -pyrrolidin- - (4-chloro-phenyl) -4-methylamino-pyrrolidine- 1-carbonyl] -3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- Carbonitrile and 4-hydroxy-benzonitrile, the title compound was obtained as colorless viscous oil. MS m / e: 569.4 [M + H] &lt; ⁺ &gt;.

Example  229

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] bipyridinyl-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  o- Tolyl  Ester

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- (3R, 4S) -3, 4-dihydro-2H-pyridin-2-ylmethoxy) - carbonyl) -pyrrolidin- - (4-chloro-phenyl) -4-methylamino-pyrrolidine- 1-carbonyl] -3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- Carbonitrile and 2-methyl-phenol, the title compound was obtained as colorless viscous oil. MS m / e: 558.4 [M + H] &lt; ⁺ &gt;.

Example  230

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] bipyridinyl-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  m- Tolyl  Ester

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- (3R, 4S) -3, 4-dihydro-2H-pyridin-2-ylmethoxy) - carbonyl) -pyrrolidin- - (4-chloro-phenyl) -4-methylamino-pyrrolidine- 1-carbonyl] -3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- Carbonitrile and 3-methyl-phenol, the title compound was obtained as colorless viscous oil. MS m / e: 558.4 [M + H] &lt; ⁺ &gt;.

Example  231

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] bipyridinyl-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid Tetrahydro -Pyran-4- Ime Tylester

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- (3R, 4S) -3, 4-dihydro-2H-pyridin-2-ylmethoxy) - carbonyl) -pyrrolidin- - (4-chloro-phenyl) -4-methylamino-pyrrolidine- 1-carbonyl] -3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- Carbonitrile and (tetrahydro-pyran-4-yl) -methanol as the colorless viscous oil. MS m / e: 566.5 [M + H] &lt; ⁺ &gt;.

Example  232

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] bipyridinyl-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid Tetrahydro - furan-2- Ime Tylester

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- (3R, 4S) -3, 4-dihydro-2H-pyridin-2-ylmethoxy) - carbonyl) -pyrrolidin- - (4-chloro-phenyl) -4-methylamino-pyrrolidine- 1-carbonyl] -3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- Carbonitrile and (tetrahydro-furan-2-yl) -methanol as the colorless viscous oil. MS m / e: 552.5 [M + H] &lt; ⁺ &gt;.

Example  233

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] bipyridinyl-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid Tetrahydro - furan-3- Ime Tylester

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- (3R, 4S) -3, 4-dihydro-2H-pyridin-2-ylmethoxy) - carbonyl) -pyrrolidin- - (4-chloro-phenyl) -4-methylamino-pyrrolidine- 1-carbonyl] -3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- Carbonitrile and (tetrahydro-furan-3-yl) -methanol as the colorless viscous oil. MS m / e: 552.5 [M + H] &lt; ⁺ &gt;.

Example  234

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] bipyridinyl-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  1,1- Dimethyl -Profile ester

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- (3R, 4S) -3, 4-dihydro-2H-pyridin-2-ylmethoxy) - carbonyl) -pyrrolidin- - (4-chloro-phenyl) -4-methylamino-pyrrolidine- 1-carbonyl] -3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- Carbonnitrile and 2-methyl-butan-2-ol, the title compound was obtained as colorless viscous oil. MS m / e: 538.4 [M + H] &lt; ⁺ &gt;.

Example  235

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] bipyridinyl-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  2,2,2- Trifluro -1,1- this Methyl-ethyl ester

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- (3R, 4S) -3, 4-dihydro-2H-pyridin-2-ylmethoxy) - carbonyl) -pyrrolidin- - (4-chloro-phenyl) -4-methylamino-pyrrolidine- 1-carbonyl] -3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- Carbonitrile and 1,1,1-trifluoro-2-methyl-propan-2-ol, the title compound was obtained as colorless viscous oil. MS m / e: 578.4 [M + H] &lt; ⁺ &gt;.

Example  236

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] bipyridinyl-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  1- (4- Fluoro - Phenyl ) -Propyl ester

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- (3R, 4S) -3, 4-dihydro-2H-pyridin-2-ylmethoxy) - carbonyl) -pyrrolidin- - (4-chloro-phenyl) -4-methylamino-pyrrolidine- 1-carbonyl] -3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- Carbonitrile and 1- (4-fluoro-phenyl) -propan-1-ol, the title compound was obtained as a pale yellow viscous oil. MS m / e: 604.4 [M + H] &lt; ⁺ &gt;.

Example  237

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] bipyridinyl-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Cyano -2- Fluoro - Phenyl  Ester

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- (3R, 4S) -3, 4-dihydro-2H-pyridin-2-ylmethoxy) - carbonyl) -pyrrolidin- - (4-chloro-phenyl) -4-methylamino-pyrrolidine- 1-carbonyl] -3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- Carbonitrile and 3-fluoro-4-hydroxy-benzonitrile, the title compound was obtained as colorless viscous oil. MS m / e: 587.2 [M + H] &lt; ⁺ &gt;.

Example  238

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] bipyridinyl-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Methoxy - Cyclohexyl s foundation

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- (3R, 4S) -3, 4-dihydro-2H-pyridin-2-ylmethoxy) - carbonyl) -pyrrolidin- - (4-chloro-phenyl) -4-methylamino-pyrrolidine- 1-carbonyl] -3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- Carbonitrile and 4-methoxy-cyclohexanol, the title compound was obtained as colorless viscous oil. MS m / e: 580.4 [M + H] &lt; ⁺ &gt;.

Example  239

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] bipyridinyl-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid Cyclopropyl -(4- Fluoro - Phenyl ) - methyl  Ester

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- (3R, 4S) -3, 4-dihydro-2H-pyridin-2-ylmethoxy) - carbonyl) -pyrrolidin- - (4-chloro-phenyl) -4-methylamino-pyrrolidine- 1-carbonyl] -3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- The title compound was obtained as colorless viscous oil from carbonitrile and cyclopropyl- (4-fluoro-phenyl) -methanol. MS m / e: 616.4 [M + H] &lt; ⁺ &gt;.

Example  240

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] bipyridinyl-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- methyl -One- Trifluoromethyl - Cyclohexyl  Ester

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- (3R, 4S) -3, 4-dihydro-2H-pyridin-2-ylmethoxy) - carbonyl) -pyrrolidin- - (4-chloro-phenyl) -4-methylamino-pyrrolidine- 1-carbonyl] -3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- Carbonitrile and 4-methyl-l-trifluoromethyl-cyclohexanol as the pale yellow viscous oil. MS m / e: 632.5 [M + H] &lt; ⁺ &gt;.

Example  241

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] bipyridinyl-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  1,4- Dimethyl - Cyclohexyl  Ester

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- (3R, 4S) -3, 4-dihydro-2H-pyridin-2-ylmethoxy) - carbonyl) -pyrrolidin- - (4-chloro-phenyl) -4-methylamino-pyrrolidine- 1-carbonyl] -3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- Carbonitrile and 1,4-dimethyl-cyclohexanol as the pale yellow viscous oil. MS m / e: 578.4 [M + H] &lt; ⁺ &gt;.

Example  242

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] bipyridinyl-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  1,4- Dimethyl - Cyclohexyl  Ester

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- (3R, 4S) -3, 4-dihydro-2H-pyridin-2-ylmethoxy) - carbonyl) -pyrrolidin- - (4-chloro-phenyl) -4-methylamino-pyrrolidine- 1-carbonyl] -3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- Carbonnitrile and l, 4-dimethyl-cyclohexanol, the title compound was obtained as colorless viscous oil. MS m / e: 578.4 [M + H] &lt; ⁺ &gt;.

Example  243

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] bipyridinyl-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  One- methyl - Cyclopentyl  Ester

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- (3R, 4S) -3, 4-dihydro-2H-pyridin-2-ylmethoxy) - carbonyl) -pyrrolidin- - (4-chloro-phenyl) -4-methylamino-pyrrolidine- 1-carbonyl] -3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- Carbonitrile and 1-methyl-cyclopentanol, the title compound was obtained as colorless viscous oil. MS m / e: 550.4 [M + H] &lt; ⁺ &gt;.

Example  244

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] bipyridinyl-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  5- Chloro -Pyridin-2-yl ester

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- (3R, 4S) -3, 4-dihydro-2H-pyridin-2-ylmethoxy) - carbonyl) -pyrrolidin- - (4-chloro-phenyl) -4-methylamino-pyrrolidine- 1-carbonyl] -3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- Carbonitrile and 5-chloro-pyridin-2-ol, the title compound was obtained as colorless viscous oil. MS m / e: 579.3 [M + H] &lt; ⁺ &gt;.

Example  245

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Cyano -3,4,5,6- Tetrahydro -2H- [1,2 '] bipyridinyl-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Cyano -3- Fluoro - Phenyl  Ester

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- (3R, 4S) -3, 4-dihydro-2H-pyridin-2-ylmethoxy) - carbonyl) -pyrrolidin- - (4-chloro-phenyl) -4-methylamino-pyrrolidine- 1-carbonyl] -3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- Carbonitrile and 2-fluoro-4-hydroxy-benzonitrile, the title compound was obtained as colorless viscous oil. MS m / e: 587.2 [M + H] &lt; ⁺ &gt;.

Example  246

[(3S, 4R) -1- (l-acetyl-piperidine-4-carbonyl) -4- Chloro - Phenyl ) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

To a solution of 94 mg (0.204 mmol) of 4-fluorophenyl (3S, 4R) -4- (4-chlorophenyl) -1- (piperidine- 4-carbonyl) pyrrolidin- (Methyl) carbamate and 132 mg (1.02 mmol) of DIPEA was added 24.1 mg (0.3 mmol) of acetyl chloride and stirred for 5 hours. Methanol was added and stirred overnight. The reaction mixture was extracted with saturated NaHCO ₃ and the aqueous layer was extracted with DCM. Dry the combined organic layers with Na ₂ SO _4, filtered, and concentrated in vacuo. The residue was purified by DCM, methanol and aqueous NH column on silica, eluting with a gradient formed from _three chromatography. The product containing fractions were evaporated to yield 53 mg (52%) of the title compound as a light yellow foam. MS m / e: 502.2 [M + H] &lt; ⁺ &gt;.

Example  247

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (1- Cyclobutanecarbonyl -Piperidine-4-carbonyl) -pyrrolidin-3-yl] - methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

To a solution of 27.6 mg (0.06 mmol) of 4-fluorophenyl (3S, 4R) -4- (4-chlorophenyl) -1- (piperidin- 4-carbonyl) pyrrolidin- (Methyl) carbamate, 0.52 mL (0.072 mmol) HATU (0.136 M in DMF), 12 mg (0.072 mmol) cyclobutanecarboxylic acid and 46.5 mg (0.36 mmol) DIPEA was shaken overnight at room temperature. The mixture was subjected to preparative HPLC chromatography on reversed phase eluting with a gradient formed from acetonitrile, water and NEt ₃ . The product containing fractions were evaporated to yield 12.5 mg (39%) of the title compound as off-white solid. MS m / e: 542.3 [M + H] &lt; ⁺ &gt;.

Example  248

{(3S, 4R) -4- (4- Chloro - Phenyl ) -1- [1- (3- methyl - Oxetane -3-carbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid &lt; / RTI &gt; (3S, 4R) -4- (4-chlorophenyl) -1- (piperidine-4-carbonyl) piperidine was prepared in analogy to the procedure for the synthesis of 4-fluoro- Yl) pyrrolidin-3-yl (methyl) carbamate and 3-methyloxetane-3-carboxylic acid. MS m / e: 558.3 [M + H] &lt; ⁺ &gt;.

Example  249

{(3S, 4R) -4- (4- Chloro - Phenyl ) -1- [1- (3- Fluoro - Cyclobutanecarbonyl ) -Piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid &lt; / RTI &gt; (3S, 4R) -4- (4-chlorophenyl) -1- (piperidine-4-carbonyl) piperidine was prepared in analogy to the procedure for the synthesis of 4-fluoro- Yl) pyrrolidin-3-yl (methyl) carbamate and 3-fluorocyclobutanecarboxylic acid. MS m / e: 560.2 [M + H] &lt; ⁺ &gt;.

Example  250

{(3S, 4R) -4- (4- Chloro - Phenyl ) -1- [1- (3,3- Difluoro - Cyclobutanecarbonyl ) -Piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid &lt; / RTI &gt; (3S, 4R) -4- (4-chlorophenyl) -1- (piperidine-4-carbonyl) piperidine was prepared in analogy to the procedure for the synthesis of 4-fluoro- Yl) pyrrolidin-3-yl (methyl) carbamate and 3,3-difluorocyclobutanecarboxylic acid. MS m / e: 578.3 [M + H] &lt; ⁺ &gt;.

Example  251

{(3S, 4R) -4- (4- Chloro - Phenyl ) -1- [1- (3- Methoxy - Cyclobutanecarbonyl ) -Piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid &lt; / RTI &gt; (3S, 4R) -4- (4-chlorophenyl) -1- (piperidine-4-carbonyl) piperidine was prepared in analogy to the procedure for the synthesis of 4-fluoro- Yl) pyrrolidin-3-yl (methyl) carbamate and 3-methoxycyclobutanecarboxylic acid. MS m / e: 572.2 [M + H] &lt; ⁺ &gt;.

Example  252

{(3S, 4R) -4- (4- Chloro - Phenyl ) -1- [1- (1- Trifluoromethyl - Cyclobutanecarbonyl ) -Piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid &lt; / RTI &gt; (3S, 4R) -4- (4-chlorophenyl) -1- (piperidine-4-carbonyl) piperidine was prepared in analogy to the procedure for the synthesis of 4-fluoro- Yl) pyrrolidin-3-yl (methyl) carbamate and 1- (trifluoromethyl) cyclobutanecarboxylic acid. MS m / e: 572.2 [M + H] &lt; ⁺ &gt;.

Example  253

{(3S, 4R) -4- (4- Chloro - Phenyl ) -1- [1- (2- Cyano -Acetyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid &lt; / RTI &gt; (3S, 4R) -4- (4-chlorophenyl) -1- (piperidine-4-carbonyl) piperidine was prepared in analogy to the procedure for the synthesis of 4-fluoro- Yl) pyrrolidin-3-yl (methyl) carbamate and 2-cyanoacetic acid. MS m / e: 572.2 [M + H] &lt; ⁺ &gt;.

Example  254

{(3S, 4R) -4- (4- Chloro - Phenyl ) -1- [1- (1- Cyano - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid &lt; / RTI &gt; (3S, 4R) -4- (4-chlorophenyl) -1- (piperidine-4-carbonyl) piperidine was prepared in analogy to the procedure for the synthesis of 4-fluoro- Yl) pyrrolidin-3-yl (methyl) carbamate and 1-cyanocyclopropanecarboxylic acid. MS m / e: 553.3 [M + H] &lt; ⁺ &gt;.

Example  255

{(3S, 4R) -4- (4- Chloro - Phenyl ) -1- [1- (1- Trifluoromethyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid &lt; / RTI &gt; (3S, 4R) -4- (4-chlorophenyl) -1- (piperidine-4-carbonyl) piperidine was prepared in analogy to the procedure for the synthesis of 4-fluoro- Yl) pyrrolidin-3-yl (methyl) carbamate and 1- (trifluoromethyl) cyclopropanecarboxylic acid. MS m / e: 596.3 [M + H] &lt; ⁺ &gt;.

Example  256

{(3S, 4R) -4- (4- Chloro - Phenyl ) -1- [1- (2,2- Difluoro - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid &lt; / RTI &gt; (3S, 4R) -4- (4-chlorophenyl) -1- (piperidine-4-carbonyl) piperidine was prepared in analogy to the procedure for the synthesis of 4-fluoro- Yl) pyrrolidin-3-yl (methyl) carbamate and 2,2-difluorocyclopropanecarboxylic acid. MS m / e: 564.3 [M + H] &lt; ⁺ &gt;.

Example  257

{(3S, 4R) -4- (4- Chloro - Phenyl ) -1- [1- ( Tetrahydro -Pyran-4-carbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid &lt; / RTI &gt; (3S, 4R) -4- (4-chlorophenyl) -1- (piperidine-4-carbonyl) piperidine was prepared in analogy to the procedure for the synthesis of 4-fluoro- Yl) pyrrolidin-3-yl (methyl) carbamate and tetrahydro-2H-pyran-4-carboxylic acid. MS m / e: 572.2 [M + H] &lt; ⁺ &gt;.

Example  258

{(3S, 4R) -4- (4- Chloro - Phenyl ) -1- [1- (2,2- Dimethyl - Tetrahydro -Pyran-4-carbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid &lt; / RTI &gt; (3S, 4R) -4- (4-chlorophenyl) -1- (piperidine-4-carbonyl) piperidine was prepared in analogy to the procedure for the synthesis of 4-fluoro- Yl) pyrrolidin-3-yl (methyl) carbamate and 2,2-dimethyltetrahydro-2H-pyran-4-carboxylic acid. MS m / e: 600.3 [M + H] &lt; ⁺ &gt;.

Example  259

{(3S, 4R) -4- (4- Chloro - Phenyl ) -1- [1- (1- Methoxymethyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid &lt; / RTI &gt; (3S, 4R) -4- (4-chlorophenyl) -1- (piperidine-4-carbonyl) piperidine was prepared in analogy to the procedure for the synthesis of 4-fluoro- Yl) pyrrolidin-3-yl (methyl) carbamate and 1- (methoxymethyl) cyclopropanecarboxylic acid. MS m / e: 572.2 [M + H] &lt; ⁺ &gt;.

Example  260

{(3S, 4R) -4- (4- Chloro - Phenyl ) -1- [1- (2,2- Dimethyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid &lt; / RTI &gt; (3S, 4R) -4- (4-chlorophenyl) -1- (piperidine-4-carbonyl) piperidine was prepared in analogy to the procedure for the synthesis of 4-fluoro- Yl) pyrrolidin-3-yl (methyl) carbamate and 2,2-dimethylcyclopropanecarboxylic acid. MS m / e: 556.2 [M + H] &lt; ⁺ &gt;.

Example  261

{(3S, 4R) -4- (4- Chloro - Phenyl ) -1- [1- (5- Trifluoromethyl -Pyridine-2-carbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid &lt; / RTI &gt; (3S, 4R) -4- (4-chlorophenyl) -1- (piperidine-4-carbonyl) piperidine was prepared in analogy to the procedure for the synthesis of 4-fluoro- Yl) pyrrolidin-3-yl (methyl) carbamate and 5- (trifluoromethyl) picolinic acid. MS m / e: 633.4 [M + H] &lt; ⁺ &gt;.

Example  262

{(3S, 4R) -4- (4- Chloro - Phenyl ) -1- [1- (5- Fluoro -Pyridine-2-carbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid &lt; / RTI &gt; (3S, 4R) -4- (4-chlorophenyl) -1- (piperidine-4-carbonyl) piperidine was prepared in analogy to the procedure for the synthesis of 4-fluoro- Yl) pyrrolidin-3-yl (methyl) carbamate and 5-fluoropicolinic acid. MS m / e: 583.2 [M + H] &lt; ⁺ &gt;.

Example  263

{(3S, 4R) -4- (4- Chloro - Phenyl ) -1- [1- (6-oxo-piperidine-3-carbonyl) -piperidine-4- carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid &lt; / RTI &gt; (3S, 4R) -4- (4-chlorophenyl) -1- (piperidine-4-carbonyl) piperidine was prepared in analogy to the procedure for the synthesis of 4-fluoro- Yl) pyrrolidin-3-yl (methyl) carbamate and 6-oxopiperidine-3-carboxylic acid. MS m / e: 585.3 [M + H] &lt; ⁺ &gt;.

Example  264

{(3S, 4R) -4- (4- Chloro - Phenyl ) -1- [1- (1-isopropyl-6-oxo-piperidine-3- carbonyl) -piperidine- Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid &lt; / RTI &gt; (3S, 4R) -4- (4-chlorophenyl) -1- (piperidine-4-carbonyl) piperidine was prepared in analogy to the procedure for the synthesis of 4-fluoro- Yl) pyrrolidin-3-yl (methyl) carbamate and 1-isopropyl-6-oxopiperidine-3-carboxylic acid. MS m / e: 627.4 [M + H] &lt; ⁺ &gt;.

Example  265

[(3S, 4R) -1- (1- Cyclobutanecarbonyl -Piperidine-4-carbonyl) -4- (3,4- Dichloro -Phenyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

4 -Chloro - phenyl ) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro- phenyl ester

To a solution of 3.35 g (10 mmol) (3S, 4R) -l-benzyl-4- (3,4-dichlorophenyl) -N-methylpyrrolidin- Example 159, h), 1.61 g (12.5 mmol) of DIPEA and 1.92 g (11 mmol) of 4-fluorophenyl chloroformate was stirred at 0 &lt; 0 &gt; C for 1 hour and evaporated to dryness. The residue was subjected to column chromatography on silica eluting with a gradient formed from heptane and t-butyl-methyl ether to give 3.07 g (65%) of the title compound as a colorless viscous oil after evaporation of the product containing fractions. MS m / e: 473.1 [M + H] &lt; ⁺ &gt;.

b) [(3S, 4R) -4- (3,4- dichloro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester

Synthesis of rac - [(3R, 4S) -4- (3,4-dichloro-phenyl) -pyrrolidin-3- yl] -methyl- carbamic acid tert- butyl ester (example 1, e) In analogy to the procedure, [(3S, 4R) -l-benzyl-4- (3,4-dichloro- phenyl) -pyrrolidin-3- yl] -methyl-carbamic acid 4-fluoro-phenyl ester The title compound was obtained, which was isolated as a brown foam. MS m / e: 383.2 [M + H] &lt; ⁺ &gt;.

c) [(3S, 4R) -4- (3,4- dichloro-phenyl) -1- (piperidin-4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4- Fluoro - phenyl ester

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- (3S, 4R) -4- (3,4-Dichloro-phenyl) -piperidine-l-carboxylic acid tert- butyl ester in analogy to the procedure for the synthesis of [ -Pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester and N-Boc-isonipecotic acid. After acidic cleavage of the Boc group with TFA, the title compound was isolated. MS m / e: 494.2 [M + H] &lt; ⁺ &gt;.

d) [(3S, 4R) -1- (1- cyclobutane-carbonyl-piperidine-4-carbonyl) -4- (3,4-dichloro-phenyl) -pyrrolidin-3-yl; -methyl-carbamic acid 4-fluoro-phenyl ester

4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid &lt; / RTI &gt; (3S, 4R) -4- (3,4-Dichloro-phenyl) -l- (piperidine-4-carbonyl) -piperidine- Yl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester and cyclobutanecarboxylic acid. MS m / e: 576.3 [M + H] &lt; ⁺ &gt;.

Example  266

{(3S, 4R) -4- (3,4- Dichloro - Phenyl ) -1- [1- (3- methyl - Oxetane -3-carbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid &lt; / RTI &gt; (3S, 4R) -4- (3,4-Dichloro-phenyl) -l- (piperidine-4-carbonyl) -piperidine- Yl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester and 3-methyloxetane-3-carboxylic acid. MS m / e: 592.3 [M + H] &lt; ⁺ &gt;.

Example  267

{(3S, 4R) -4- (3,4- Dichloro - Phenyl ) -1- [1- (3- Fluoro - Cyclobutanecarbonyl ) -Piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid &lt; / RTI &gt; (3S, 4R) -4- (3,4-Dichloro-phenyl) -l- (piperidine-4-carbonyl) -piperidine- Yl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester and 3-fluorocyclobutanecarboxylic acid. MS m / e: 594.3 [M + H] &lt; ⁺ &gt;.

Example  268

{(3S, 4R) -4- (3,4- Dichloro - Phenyl ) -1- [1- (3,3- Difluoro - Cyclobutanecarbonyl ) -Piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid &lt; / RTI &gt; (3S, 4R) -4- (3,4-Dichloro-phenyl) -l- (piperidine-4-carbonyl) -piperidine- Yl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester and 3,3-difluorocyclobutanecarboxylic acid. MS m / e: 612.2 [M + H] &lt; ⁺ &gt;.

Example  269

{(3S, 4R) -4- (3,4- Dichloro - Phenyl ) -1- [1- (3- Methoxy - Cyclobutanecarbonyl ) -Piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid &lt; / RTI &gt; (3S, 4R) -4- (3,4-Dichloro-phenyl) -l- (piperidine-4-carbonyl) -piperidine- Yl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester and 3-methoxycyclobutanecarboxylic acid. MS m / e: 606.3 [M + H] &lt; ⁺ &gt;.

Example  270

{(3S, 4R) -4- (3,4- Dichloro - Phenyl ) -1- [1- (1- Trifluoromethyl - Cyclobutanecarbonyl ) -Piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid &lt; / RTI &gt; (3S, 4R) -4- (3,4-Dichloro-phenyl) -l- (piperidine-4-carbonyl) -piperidine- Yl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester and 1- (trifluoromethyl) cyclobutanecarboxylic acid. MS m / e: 644.2 [M + H] &lt; ⁺ &gt;.

Example  271

[(3S, 4R) -1- [1- (2- Cyano -Acetyl) -piperidine-4-carbonyl] -4- (3,4- Dichloro - Phenyl ) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid &lt; / RTI &gt; (3S, 4R) -4- (3,4-Dichloro-phenyl) -l- (piperidine-4-carbonyl) -piperidine- Yl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester and 2-cyanoacetic acid. MS m / e: 561.1 [M + H] &lt; ⁺ &gt;.

Example  272

[(3S, 4R) -1- [1- (1- Cyano - cyclopropanecarbonyl) -piperidine-4-carbonyl] -4- (3,4-di Eclipse Roro - Phenyl ) - Pyrrolidine -3 days]- methyl - Carbamic acid 4 - Fluoro - Phenyl  Ester

4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid &lt; / RTI &gt; (3S, 4R) -4- (3,4-Dichloro-phenyl) -l- (piperidine-4-carbonyl) -piperidine- Yl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester and 1-cyanocyclopropanecarboxylic acid. MS m / e: 587.1 [M + H] &lt; ⁺ &gt;.

Example  273

{(3S, 4R) -4- (3,4- Dichloro - Phenyl ) -1- [1- (1- Trifluoromethyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid &lt; / RTI &gt; (3S, 4R) -4- (3,4-Dichloro-phenyl) -l- (piperidine-4-carbonyl) -piperidine- Yl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester and 1- (trifluoromethyl) cyclopropanecarboxylic acid. MS m / e: 630.4 [M + H] &lt; ⁺ &gt;.

Example  274

{(3S, 4R) -4- (3,4- Dichloro - Phenyl ) -1- [1- (2,2- Difluoro - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid &lt; / RTI &gt; (3S, 4R) -4- (3,4-Dichloro-phenyl) -l- (piperidine-4-carbonyl) -piperidine- Yl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester and 2,2-difluorocyclopropanecarboxylic acid. MS m / e: 598.1 [M + H] &lt; ⁺ &gt;.

Example  275

{(3S, 4R) -4- (3,4- Dichloro - Phenyl ) -1- [1- ( Tetrahydro -Pyran-4-carbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid &lt; / RTI &gt; (3S, 4R) -4- (3,4-Dichloro-phenyl) -l- (piperidine-4-carbonyl) -piperidine- Yl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester and tetrahydro-2H-pyran-4-carboxylic acid. MS m / e: 606.2 [M + H] &lt; ⁺ &gt;.

Example  276

{(3S, 4R) -4- (3,4- Dichloro - Phenyl ) -1- [1- (2,2- Dimethyl - Tetrahydro -Pyran-4-carbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid &lt; / RTI &gt; (3S, 4R) -4- (3,4-Dichloro-phenyl) -l- (piperidine-4-carbonyl) -piperidine- Yl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester and 2,2-dimethyltetrahydro-2H-pyran-4-carboxylic acid. MS m / e: 634.2 [M + H] &lt; ⁺ &gt;.

Example  277

{(3S, 4R) -4- (3,4- Dichloro - Phenyl ) -1- [1- (1- Methoxymethyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid &lt; / RTI &gt; (3S, 4R) -4- (3,4-Dichloro-phenyl) -l- (piperidine-4-carbonyl) -piperidine- Yl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester and 1- (methoxymethyl) cyclopropanecarboxylic acid. MS m / e: 606.3 [M + H] &lt; ⁺ &gt;.

Example  278

{(3S, 4R) -4- (3,4- Dichloro - Phenyl ) -1- [1- (2,2- Dimethyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid &lt; / RTI &gt; (3S, 4R) -4- (3,4-Dichloro-phenyl) -l- (piperidine-4-carbonyl) -piperidine- Yl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester and 2,2-dimethylcyclopropanecarboxylic acid. MS m / e: 590.2 [M + H] &lt; ⁺ &gt;.

Example  279

{(3S, 4R) -4- (3,4- Dichloro - Phenyl ) -1- [1- (5- Trifluoromethyl -Pyridine-2-carbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid &lt; / RTI &gt; (3S, 4R) -4- (3,4-Dichloro-phenyl) -l- (piperidine-4-carbonyl) -piperidine- Yl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester and 5- (trifluoromethyl) picolinic acid. MS m / e: 667.2 [M + H] &lt; ⁺ &gt;.

Example  280

{(3S, 4R) -4- (3,4- Dichloro - Phenyl ) -1- [1- (5- Fluoro -Pyridine-2-carbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid &lt; / RTI &gt; (3S, 4R) -4- (3,4-Dichloro-phenyl) -l- (piperidine-4-carbonyl) -piperidine- Yl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester and 5-fluoropicolic acid. MS m / e: 617.3 [M + H] &lt; ⁺ &gt;.

Example  281

{(3S, 4R) -4- (3,4- Dichloro - Phenyl ) -1- [1- (6-oxo-piperidine-3-carbonyl) -piperidine-4- carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid &lt; / RTI &gt; (3S, 4R) -4- (3,4-Dichloro-phenyl) -l- (piperidine-4-carbonyl) -piperidine- Yl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester and 6-oxopiperidine-3-carboxylic acid. MS m / e: 619.4 [M + H] &lt; ⁺ &gt;.

Example  282

{(3S, 4R) -4- (3,4- Dichloro - Phenyl ) -1- [1- (1-isopropyl-6-oxo-piperidine-3- carbonyl) -piperidine- Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid &lt; / RTI &gt; (3S, 4R) -4- (3,4-Dichloro-phenyl) -l- (piperidine-4-carbonyl) -piperidine- Yl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester and l-isopropyl-6-oxopiperidine-3-carboxylic acid. MS m / e: 661.3 [M + H] &lt; ⁺ &gt;.

Example  283

[(3S, 4R) -1- (l-acetyl-piperidine-4-carbonyl) -4- Dichloro - Phenyl ) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

4-carbonyl) -4- (4-chloro-phenyl) -pyrrolidin-3- yl] -methyl-carbamic acid 4- fluoro (3S, 4R) -4- (3,4-Dichloro-phenyl) -l- (piperidine-4-carbonyl) - Pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester and acetyl chloride gave the title compound. MS m / e: 536.1 [M + H] &lt; ⁺ &gt;.

Example  284

[(3S, 4R) -1- [1- (2- Cyano -Acetyl) -piperidine-4-carbonyl] -4- (4- Fluoro - Phenyl ) -Pyrrolidin-3-yl] - methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

4- fluoro - phenyl ) -pyrrolidin- 3 - yl] -methyl - carbamic acid 4- fluoro - phenyl ester

Methyl-carbamic acid 4-fluoro-phenyl ester (example 265, a (4-Chloro-phenyl) -pyrrolidin- (WO2008128891) and 4 (4-fluoro-phenyl) -pyrrolidin-3-yl] -methyl- amine in analogy to the procedure for the synthesis of rac - [(3S, - fluorophenyl chloroformate. &Lt; / RTI &gt; MS m / e: 423.3 [M + H] &lt; ⁺ &gt;. It was then subjected to column chromatography on Chiralpak AD eluting with a gradient formed from ethanol and heptane. The product containing fractions were evaporated to give the title compound as an off-white solid. MS m / e: 423.3 [M + H] &lt; ⁺ &gt;.

b) [(3S, 4R) -4- ( 4-fluorophenyl) -1- (piperidin-4-carbonyl) -pyrrolidin-3-yl] - carbamic acid with 4-fluoro-methyl - phenyl ester

Synthesis of rac - [(3R, 4S) -4- (3,4-dichloro-phenyl) -pyrrolidin-3- yl] -methyl- carbamic acid tert- butyl ester (example 1, e) Benzyl group was prepared from [(3S, 4R) -l-benzyl-4- (4-fluoro-phenyl) -pyrrolidin-3- yl] -methyl-carbamic acid 4-fluoro- C to give the title compound and give rac - {(3R, 4S) -4- (3,4-dichloro-phenyl) -l- 4-carbonyl] -pyrrolidin-3-yl} -methyl-carbamic acid tert-butyl ester (example 1, -Fluoro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester and N-Boc-isonipecotic acid. The title compound was then isolated after acidic cleavage of the Boc group with TFA. MS m / e: 444.3 [M + H] &lt; ⁺ &gt;.

c) [(3S, 4R) -1- [1- (2- cyano-acetyl) -piperidine-4-carbonyl] -4- (4-fluoro-phenyl) -pyrrolidin-3 Yl] -methyl - carbamic acid 4- fluoro - phenyl ester

4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid &lt; / RTI &gt; (3S, 4R) -4- (4-fluoro-phenyl) -l- (piperidine-4-carbonyl) -piperidine- -Pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester and 2-cyanoacetic acid. MS m / e: 511.4 [M + H] &lt; ⁺ &gt;.

Example  285

[(3S, 4R) -1- (l-acetyl-piperidine-4-carbonyl) -4- Fluoro - Phenyl ) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid &lt; / RTI &gt; (3S, 4R) -4- (4-fluoro-phenyl) -l- (piperidine-4-carbonyl) -piperidine- -Pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester and acetic acid. MS m / e: 486.4 [M + H] &lt; ⁺ &gt;.

Example  286

{(3S, 4R) -4- (4- Fluoro - Phenyl ) -1- [1- (3- methyl - Oxetane -3-carbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid &lt; / RTI &gt; (3S, 4R) -4- (4-fluoro-phenyl) -l- (piperidine-4-carbonyl) -piperidine- -Pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester and 3-methyloxetane-3-carboxylic acid. MS m / e: 542.3 [M + H] &lt; ⁺ &gt;.

Example  287

[(3S, 4R) -1- [1- (3- Fluoro - Cyclobutanecarbonyl ) -Piperidine-4-carbonyl] -4- (4-fluoro- Phenyl ) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid &lt; / RTI &gt; (3S, 4R) -4- (4-fluoro-phenyl) -l- (piperidine-4-carbonyl) -piperidine- -Pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester and 3-fluorocyclobutanecarboxylic acid. MS m / e: 544.4 [M + H] &lt; ⁺ &gt;.

Example  288

[(3S, 4R) -1- [1- (1- Cyano - cyclopropanecarbonyl) -piperidine-4-carbonyl] -4- (4-fluoro- Phenyl ) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid &lt; / RTI &gt; (3S, 4R) -4- (4-fluoro-phenyl) -l- (piperidine-4-carbonyl) -piperidine- -Pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester and 1-cyanocyclopropanecarboxylic acid. MS m / e: 537.3 [M + H] &lt; ⁺ &gt;.

Example  289

{(3S, 4R) -4- (4- Fluoro - Phenyl ) -1- [1- (1- Trifluoromethyl - Cyclobutanecarbonyl ) -Piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid &lt; / RTI &gt; (3S, 4R) -4- (4-fluoro-phenyl) -l- (piperidine-4-carbonyl) -piperidine- -Pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester and 1- (trifluoromethyl) cyclobutanecarboxylic acid. MS m / e: 594.3 [M + H] &lt; ⁺ &gt;.

Example  290

{(3S, 4R) -4- (4- Fluoro - Phenyl ) -1- [1- (5- Trifluoromethyl -Pyridine-2-carbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid &lt; / RTI &gt; (3S, 4R) -4- (4-fluoro-phenyl) -l- (piperidine-4-carbonyl) -piperidine- -Pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester and 5- (trifluoromethyl) picolinic acid. MS m / e: 617.4 [M + H] &lt; ⁺ &gt;.

Example  291

{(3S, 4R) -4- (4- Fluoro - Phenyl ) -1- [1- (6-oxo-piperidine-3-carbonyl) -piperidine-4- carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid &lt; / RTI &gt; (3S, 4R) -4- (4-fluoro-phenyl) -l- (piperidine-4-carbonyl) -piperidine- -Pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester and 6-oxopiperidine-3-carboxylic acid. MS m / e: 569.3 [M + H] &lt; ⁺ &gt;.

Example  292

{(3S, 4R) -4- (3,4- Dichloro - Phenyl ) -1- [1 - ((S) -4-oxo- Azetidine -2-carbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid &lt; / RTI &gt; (3S, 4R) -4- (3,4-Dichloro-phenyl) -l- (piperidine-4-carbonyl) -piperidine- Yl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester and (S) -4-oxoazetidine-2-carboxylic acid. MS m / e: 591.3 [M + H] &lt; ⁺ &gt;.

Example  293

{(3S, 4R) -4- (3,4- Dichloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  2- Fluoro -Pyridin-3-yl ester

a) [(3S, 4R) -1- benzyl-4- (3,4-dichloro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid tert-butyl ester

To a solution of 5.96 g (17.8 mmol) (3S, 4R) -l-benzyl-4- (3,4-dichlorophenyl) -N-methylpyrrolidin- g (19.6 mmol) of di-tert-butyloxycarbonyl and 21.7 mg (0.17 mmol) of DMAP was stirred at room temperature for 45 minutes and evaporated to dryness. The residue was subjected to column chromatography on silica eluting with a gradient of heptane and i-propanol to give 5.22 g (67%) of the title compound as a yellow oil after evaporation of the product containing fractions. MS m / e: 435.1 [M + H] &lt; ⁺ &gt;.

b) [(3R, 4S) -3- (3,4- dichloro-phenyl) -4-methylamino-pyrrolidin-1-yl] - [1- (1-methyl-cyclohex yl propan-carbonyl) - Piperidin-4-yl] -methanone & lt ; / RTI & gt;

Synthesis of rac - [(3R, 4S) -4- (3,4-dichloro-phenyl) -pyrrolidin-3- yl] -methyl- carbamic acid tert- butyl ester (example 1, e) Benzyl group was prepared from [(3S, 4R) -l-benzyl-4- (3,4-dichloro- phenyl) -pyrrolidin-3- yl] -methyl- carbamic acid tert- butyl ester C to give the title compound and give rac - {(3R, 4S) -4- (3,4-dichloro-phenyl) -l- (3S, 4R) - (4-chloro-pyridin-2-yl) -carbamic acid tert- Butyl ester and 1- (1-methyl-cyclopropanecarbonyl) -piperidin-4-ylmethyl-carbamic acid tert- -Bis-protected &lt; / RTI &gt; title compound from the carboxylic acid. The title compound was then isolated after acidic cleavage of the Boc group with TFA. MS m / e: 438.1 [M + H] &lt; ⁺ &gt;.

c) {(3S, 4R) -4- (3,4- dichloro-phenyl) -1- [1- (1-cyclopenten one propane-carbonyl) -piperidine-4-carbonyl] -pyrrolidin Pyridin - 3 - yl} -methyl - carbamic acid 2- fluoro -pyridin-3-yl ester

To a solution of 50 mg (0.11 mmol) of [(3R, 4S) -3- (3,4-dichloro-phenyl) -4-methylamino-pyrrolidin- A mixture of 16.2 mg (0.12 mmol) of DIPEA and 11.8 mg (0.04 mmol) of the triphosgene was stirred for 2 hours at &lt; RTI ID = 0.0 &gt; 0-5 &lt; 0 &gt; C, concentrated in vacuo and dissolved in 1 mL DMF. A solution of 65.5 mg (0.57 mmol) 2-fluoropyridin-3-ol in 1 mL DMF was treated with 18.2 mg (0.45 mmol) NaH (55%) in mineral oil and heated to 45 C for 1 h. This solution was added to the activated amine in DMF and the mixture was shaken at 80 DEG C for 90 minutes. The mixture was filtered and the filtrate was purified by preparative HPLC on reversed phase eluting with a gradient formed from acetonitrile, water and NEt ₃ . The product containing fractions were evaporated to yield 42 mg (64%) of the title compound as off-white foam. MS m / e: 577.3 [M + H] &lt; ⁺ &gt;.

Example  294

{(3S, 4R) -4- (3,4- Dichloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  2,6- Dimethyl -Pyridin-4-yl ester

(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [1- (1- methyl- cyclopropanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid 2-fluoro-pyridin-3-yl ester (example 293) Phenyl) -4-methylamino-pyrrolidin- 1 -yl] - [1- (1 -methyl- cyclopropanecarbonyl) -piperidin-4-yl] -methanone, -Dimethylpyridin-4-ol. &Lt; / RTI &gt; MS m / e: 587.2 [M + H] &lt; ⁺ &gt;.

Example  295

{(3S, 4R) -4- (3,4- Dichloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  Pyridin-3-yl ester

(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [1- (1- methyl- cyclopropanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid 2-fluoro-pyridin-3-yl ester (example 293) Phenyl) -4-methylamino-pyrrolidin-l-yl] - [1- (1- methyl- cyclopropanecarbonyl) -piperidin- -Ol. &Lt; / RTI &gt; MS m / e: 559.3 [M + H] &lt; ⁺ &gt;.

Example  296

{(3S, 4R) -4- (3,4- Dichloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  6- methyl -Pyridin-3-yl ester

(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [1- (1- methyl- cyclopropanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid 2-fluoro-pyridin-3-yl ester (example 293) Yl) -methanone and a mixture of the triphosgene and 6-methyl (2-methyl-piperazin-1 -yl) -piperidin- Pyridin-3-ol. &Lt; / RTI &gt; MS m / e: 573.2 [M + H] &lt; ⁺ &gt;.

Example  297

{(3S, 4R) -4- (3,4- Dichloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  Pyridin-4-yl ester

(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [1- (1- methyl- cyclopropanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid 2-fluoro-pyridin-3-yl ester (example 293) Yl] -methanone, triphosgene and pyridine-4 (4-fluoro-phenyl) -4-methylamino-pyrrolidin- -Ol. &Lt; / RTI &gt; MS m / e: 559.3 [M + H] &lt; ⁺ &gt;.

Example  298

{(3S, 4R) -4- (3,4- Dichloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  2,6- Dimethyl -Pyridin-3-yl ester

(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [1- (1- methyl- cyclopropanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid 2-fluoro-pyridin-3-yl ester (example 293) Phenyl) -4-methylamino-pyrrolidin- 1 -yl] - [1- (1 -methyl- cyclopropanecarbonyl) -piperidin-4-yl] -methanone and 2,6 -Dimethylpyridin-3-ol. &Lt; / RTI &gt; MS m / e: 587.2 [M + H] &lt; ⁺ &gt;.

Example  299

{(3S, 4R) -4- (3,4- Dichloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  5- Fluoro -Pyridin-3-yl ester

(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [1- (1- methyl- cyclopropanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid 2-fluoro-pyridin-3-yl ester (example 293) Phenyl) -4-methylamino-pyrrolidin- 1 -yl] - [1- (1 -methyl- cyclopropanecarbonyl) -piperidin-4-yl] -methanone, The title compound was obtained from pyridin-3-ol. MS m / e: 577.3 [M + H] &lt; ⁺ &gt;.

Example  300

{(3S, 4R) -4- (3,4- Dichloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  6- Chloro -Pyridin-2-yl ester

(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [1- (1- methyl- cyclopropanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid 2-fluoro-pyridin-3-yl ester (example 293) Phenyl) -4-methylamino-pyrrolidin- 1 -yl] - [1- (1 -methyl- cyclopropanecarbonyl) -piperidin- 4-yl] -methanone, Pyridine-2-ol. &Lt; / RTI &gt; MS m / e: 595.2 [M + H] &lt; ⁺ &gt;.

Example  301

{(3S, 4R) -4- (3,4- Dichloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  2- Chloro -5- Fluoro -Pyridin-3-yl ester

(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [1- (1- methyl- cyclopropanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid 2-fluoro-pyridin-3-yl ester (example 293) was prepared in analogy to the synthetic procedure using [(3R, ) -4-methylamino-pyrrolidin-l-yl] - [1- (1- methyl- cyclopropanecarbonyl) -piperidin- The title compound was obtained from 5-fluoropyridin-3-ol. MS m / e: 613.1 [M + H] &lt; ⁺ &gt;.

Example  302

{(3S, 4R) -4- (3,4- Dichloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  2- Chloro -Pyridin-3-yl ester

(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [1- (1- methyl- cyclopropanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid 2-fluoro-pyridin-3-yl ester (example 293) Phenyl) -4-methylamino-pyrrolidin- 1 -yl] - [1- (1 -methyl- cyclopropanecarbonyl) -piperidin-4-yl] -methanone, Pyridin-3-ol. &Lt; / RTI &gt; MS m / e: 595.2 [M + H] &lt; ⁺ &gt;.

Example  303

{(3S, 4R) -4- (3,4- Dichloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  6- Trifluoromethyl -Pyridin-3-yl ester

(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [1- (1- methyl- cyclopropanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid 2-fluoro-pyridin-3-yl ester (example 293) Phenyl) -4-methylamino-pyrrolidin- 1 -yl] - [1- (1 -methyl- cyclopropanecarbonyl) -piperidin-4-yl] -methanone, Trifluoromethyl) pyridin-3-ol. &Lt; / RTI &gt; MS m / e: 627.2 [M + H] &lt; ⁺ &gt;.

Example  304

{(3S, 4R) -4- (3,4- Dichloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  2- Cyano -Pyridin-3-yl ester

(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [1- (1- methyl- cyclopropanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid 2-fluoro-pyridin-3-yl ester (example 293) Phenyl) -4-methylamino-pyrrolidin- 1 -yl] - [1- (1 -methyl- cyclopropanecarbonyl) -piperidin-4-yl] -methanone, triphosgene and 3- The title compound was obtained from riccipiocoloronitrile. MS m / e: 584.2 [M + H] &lt; ⁺ &gt;.

Example  305

{(3S, 4R) -4- (3,4- Dichloro - Phenyl ) -1- [1- (1- methyl - cyclopropanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  2- Fluoro -6- methyl -Pyridin-3-yl ester

(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [1- (1- methyl- cyclopropanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid 2-fluoro-pyridin-3-yl ester (example 293) Phenyl) -4-methylamino-pyrrolidin- 1 -yl] - [1- (1 -methyl- cyclopropanecarbonyl) -piperidin-4-yl] -methanone, triphosgene and 2- Methyl-pyridin-3-ol &lt; / RTI &gt; MS m / e: 591.3 [M + H] &lt; ⁺ &gt;.

Example  306

[(3S, 4R) -4- (3,4- Dichloro - Phenyl ) -1- (5'- Trifluoromethyl -3,4,5,6- Tetrahydro -2H- [1,2 '] Bipyridinyl Carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

To a solution of 100 mg (0.2 mmol) of [(3S, 4R) -4- (3,4-dichloro-phenyl) -l- (piperidine-4-carbonyl) -pyrrolidin- Bromo-5- (trifluoromethyl) pyridine and 131 mg (1 mmol) of 4-fluoro-phenyl ester, Example 265, ) Of DIPEA was heated to 80 &lt; 0 &gt; C for 18 hours. The mixture was evaporated and the residue was subjected to column chromatography on silica eluting with a gradient from ethyl acetate and heptane to give 70 mg (54%) of the title compound as a white foam after evaporation of the fractions containing the product. MS m / e: 639.1 [M + H] &lt; ⁺ &gt;.

Example  307

[(3S, 4R) -1- (5'-Acetyl-3,4,5,6- Tetrahydro -2H- [1,2 '] Bipyridinyl -4-carbonyl) -4- (3,4- Dichloro - Phenyl ) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

[(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- (5 ' -trifluoromethyl-3,4,5,6-tetrahydro- (3S, 4R) - (2-methyl-pyridin-4-yl) -pyrrolidin-3- yl] -methyl- carbamic acid 4-fluoro-phenyl ester Methyl-carbamic acid 4-fluoro-phenyl ester (example 265 (4-Chloro-phenyl) , c) and l- (6-bromopyridin-3-yl) ethanone. MS m / e: 613.2 [M + H] &lt; ⁺ &gt;.

Example  308

[(3S, 4R) -1- (5 ' - Chloro -3,4,5,6- Tetrahydro -2H- [1,2 '] Bipyridinyl -4-carbonyl) -4- (3,4- Dichloro - Phenyl ) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- (3S, 4R) -4- (4-fluoro-phenyl) -pyridin-2-ylamine in analogy to the procedure for the synthesis of [ Methyl-carbamic acid 4-fluoro-phenyl ester and 1- (5-chloropyridin-2-yl) piperidine-4-carboxylic acid. MS m / e: 605.2 [M + H] &lt; ⁺ &gt;.

Example  309

[(3S, 4R) -4- (3,4- Dichloro - Phenyl ) -1- (5'- Fluoro -3,4,5,6- Tetrahydro -2H- [1,2 '] bipyridinyl-4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- (3S, 4R) -4- (4-fluoro-phenyl) -pyridin-2-ylamine in analogy to the procedure for the synthesis of [ Yl] -methyl-carbamic acid 4-fluoro-phenyl ester and 5'-fluoro-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carboxylic acid. &Lt; / RTI &gt; MS m / e: 589.1 [M + H] &lt; ⁺ &gt;.

Example  310

[(3S, 4R) -1- (5 ' - Carbamoyl -3,4,5,6- Tetrahydro -2H- [1,2 '] Bipyridinyl -4-carbonyl) -4- (3,4- Dichloro - Phenyl ) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- (3S, 4R) -4- (4-fluoro-phenyl) -pyridin-2-ylamine in analogy to the procedure for the synthesis of [ Yl] -methyl-carbamic acid 4-fluoro-phenyl ester and 5'-carbamoyl-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carboxylic acid. &Lt; / RTI &gt; MS m / e: 614.1 [M + H] &lt; ⁺ &gt;.

Example  311

[(3S, 4R) -4- (4- Chloro -3- Fluoro - Phenyl ) -1- (5'- Fluoro -3,4,5,6- Tetrahydro -2H- [1,2 '] Bipyridinyl Carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

a) (3S, 4R) -1- benzyl-4- (4-chloro-3-fluoro-phenyl) -pyrrolidine-3-carboxylic acid Methyl ester

In analogy to the procedure for the synthesis of (3S, 4R) -l-benzyl-4- (4-chloro-phenyl) -pyrrolidine-3- carboxylic acid methyl ester (example 89, ), &Lt; / RTI &gt; the title compound was obtained. MS m / e: 348.2 [M + H] &lt; ⁺ &gt;.

b) (3S, 4R) -1- benzyl-4- (4-chloro-3-fluoro-phenyl) -pyrrolidine-3-carboxylic acid

To a solution of 19.5 g (56 mmol) of (3S, 4R) -l-benzyl-4- (4-chloro-3-fluoro- phenyl) -pyrrolidin- carboxylic acid a mixture of LiOH and H ₂ O of the methyl ester and 14.1 g (337 mmol) was heated to 80 ℃ for 45 minutes. The organic solvent was removed in vacuo and the aqueous phase was acidified with 2N HCl to pH 1-2. The precipitate was filtered, washed with acetonitrile and dried to give 15.1 g (73%) of the title compound as an off-white solid. MS m / e: 334.1 [M + H] &lt; ⁺ &gt;.

c) [(3S, 4R) -1- benzyl-4- (4-chloro-3-fluoro-phenyl) -pyrrolidin-3-yl] -carbamic acid tert-butyl ester

To a solution of 15.1 g (41 mmol) of (3S, 4R) -l-benzyl-4- (4-chloro-3-fluoro- phenyl) -pyrrolidine- mmol) in DIPEA was heated to 55 &lt; 0 &gt; C and 12.4 g (45 mmol) of diphenylphosphoryl azide was added. The mixture was heated to 80 &lt; 0 &gt; C for 3 hours and evaporated. The residue was subjected to column chromatography on silica eluting with a gradient from ethyl acetate and heptane to give 5.7 g (34%) of the title compound as an off-white solid after evaporation of the product containing fractions. MS m / e: 405.3 [M + H] &lt; ⁺ &gt;.

d) [(3S, 4R) -1- benzyl-4- (4-chloro-3-fluoro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid tert-butyl ester

To a solution of 5.7 g (14.1 mmol) of [(3S, 4R) -l-benzyl-4- (4-chloro-3-fluoro- phenyl) -pyrrolidin- Ester, 676 mg (17 mmol) NaH (55%) was stirred at room temperature for 20 min and at 60 <0> C for 1 h. 3 g (21 mmol) of iodomethane in DMF were added and the mixture was stirred at 60 &lt; 0 &gt; C for 1 h and evaporated. The residue was taken up in ethyl acetate and water, and the organic layer was washed with brine and back-extracted with ethyl acetate. Dry the combined organic layers with Na ₂ SO ₄ and, filtered and evaporated. The residue was taken up in isolut and chromatographed on silica eluting with a gradient from ethyl acetate and heptane to give 2.67 g (45%) of the title compound as a pale yellow oil after evaporation of the product containing fractions. MS m / e: 419.2 [M + H] &lt; ⁺ &gt;.

e) [(3S, 4R) -4- ( 4-chloro-3-fluoro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester

(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [1- (1- methyl- cyclopropanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 4-yl} -methyl-carbamic acid 2-fluoro-pyridin-3-yl ester (example 293c) The acid-cleaved group of the Boc-protected group with 4-fluorophenol from the 3-fluoro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid tert- Mate. Synthesis of rac - [(3R, 4S) -4- (3,4-dichloro-phenyl) -pyrrolidin-3- yl] -methyl- carbamic acid tert- butyl ester (example 1, e) (3S, 4R) -l-Benzyl-4- (4-chloro-3-fluoro-phenyl) -pyrrolidin-3- yl] -methyl- carbamic acid 4- Fluoro-phenyl ester, the title compound was obtained. MS m / e: 367.0 [M + H] &lt; ⁺ &gt;.

f) [(3S, 4R) -4- ( 4-chloro-3-fluorophenyl) -1- (3,4,5,6-tetrahydro -2H- [1,2 5'-fluoro ] Bipyridinyl- 4-carbonyl) -pyrrolidin- 3 - yl] -methyl - carbamic acid 4- fluoro - phenyl ester

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- (3S, 4R) -4- (4-chloro-3-fluoro-benzyl) -carbamic acid tert- butyl ester (example 1, Phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester and 1- (5-fluoropyridin-2-yl) piperidine-4-carboxylic acid . MS m / e: 573.1 [M + H] &lt; ⁺ &gt;.

Example  312

[(3S, 4R) -4- (4- Chloro -3- Fluoro - Phenyl ) -1- (5'- Chloro -3,4,5,6- Tetrahydro -2H- [1,2 '] Bipyridinyl Carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- (3S, 4R) -4- (4-chloro-3-fluoro-benzyl) -carbamic acid tert- butyl ester (example 1, Phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester and 1- (5-chloropyridin-2-yl) piperidine-4-carboxylic acid. MS m / e: 589.2 [M + H] &lt; ⁺ &gt;.

Example  313

[(3S, 4R) -4- (4- Chloro -3- Fluoro - Phenyl ) -1- (5'- Trifluoromethyl -3,4,5,6-tetrahydro-2H- [l, 2 ' Bipyridinyl Carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  4-fluoro- Phenyl  Ester

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- (3S, 4R) -4- (4-chloro-3-fluoro-benzyl) -carbamic acid tert- butyl ester (example 1, Phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester and 1- (5- (trifluoromethyl) pyridin- Lt; / RTI &gt; MS m / e: 623.2 [M + H] &lt; ⁺ &gt;.

Example  314

[(3S, 4R) -1- (5'-Acetyl-3,4,5,6- Tetrahydro -2H- [1,2 '] Bipyridinyl -4-carbonyl) -4- (4- Chloro -3- Fluoro - Phenyl ) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- (3S, 4R) -4- (4-chloro-3-fluoro-benzyl) -carbamic acid tert- butyl ester (example 1, Phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester and 1- (5-acetylpyridin-2- yl) piperidine-4-carboxylic acid. MS m / e: 597.2 [M + H] &lt; ⁺ &gt;.

Example  315

[(3S, 4R) -4- (3- Chloro -4- Fluoro - Phenyl ) -1- (5'- Fluoro -3,4,5,6- Tetrahydro -2H- [1,2 '] Bipyridinyl Carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

a) [(3S, 4R) -4- (3- chloro-4-fluoro-phenyl) -pyrrolidin-3-yl] - carbamic acid with 4-fluoro-phenyl methyl ester

4-fluoro-phenyl ester (example 311, e) was reacted with 4- [(3S, 4R) -4- (4-chloro-3-fluoro- phenyl) -pyrrolidin- Similar to the procedure for synthesis, the title compound was obtained as an amorphous brown solid.

b) [(3S, 4R) -4- ( 3-chloro-4-fluorophenyl) -1- (3,4,5,6-tetrahydro -2H- [1,2 5'-fluoro ] Bipyridinyl- 4-carbonyl) -pyrrolidin- 3 - yl] -methyl - carbamic acid 4- fluoro - phenyl ester

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- (3S, 4R) -4- (3-Chloro-4-fluoro-benzyl) -carbamic acid tert- butyl ester (example 1, Phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester and 1- (5-fluoropyridin-2- yl) piperidine- . MS m / e: 573.2 [M + H] &lt; ⁺ &gt;.

Example  316

[(3S, 4R) -4- (3- Chloro -4- Fluoro - Phenyl ) -1- (5'- Chloro -3,4,5,6- Tetrahydro -2H- [1,2 '] Bipyridinyl Carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- (3S, 4R) -4- (3-Chloro-4-fluoro-benzyl) -carbamic acid tert-butyl ester, Phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester and 1- (5-chloropyridin-2-yl) piperidine-4-carboxylic acid. MS m / e: 589.2 [M + H] &lt; ⁺ &gt;.

Example  317

[(3S, 4R) -4- (3- Chloro -4- Fluoro - Phenyl ) -1- (5'- Trifluoromethyl -3,4,5,6-tetrahydro-2H- [l, 2 ' Bipyridinyl Carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  4-fluoro- Phenyl  Ester

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- (3S, 4R) -4- (3-Chloro-4-fluoro-benzyl) -carbamic acid tert-butyl ester, Phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester and 1- (5- (trifluoromethyl) pyridin- Lt; / RTI &gt; MS m / e: 623.3 [M + H] &lt; ⁺ &gt;.

Example  318

[(3S, 4R) -1- (5'-Acetyl-3,4,5,6- Tetrahydro -2H- [1,2 '] Bipyridinyl -4-carbonyl) -4- (3- Chloro -4- Fluoro - Phenyl ) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- (Example 1, f) was reacted with [(3S, 4R) -4- (3-chloro-4-fluoro-phenyl) -pyridin- ) -Pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester and 1- (5-acetylpyridin-2- yl) piperidine-4-carboxylic acid. MS m / e: 597.3 [M + H] &lt; ⁺ &gt;.

Example  319

{(3S, 4R) -4- (4- Chloro - Phenyl ) -1- [1 - ((S) -4-oxo- Azetidine -2-carbonyl) -piperidine-4-carbonyl] - Pyrrolidine -3 days}- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid &lt; / RTI &gt; (3S, 4R) -4- (4-chlorophenyl) -1- (piperidine-4-carbonyl) piperidine was prepared in analogy to the procedure for the synthesis of 4-fluoro- Yl) pyrrolidin-3-yl (methyl) carbamate and (S) -4-oxoazetidine-2-carboxylic acid. MS m / e: 557.0 [M + H] &lt; ⁺ &gt;.

Example  320

[(3S, 4R) -4- (4- Chloro - Phenyl ) -1- (5'- Hydroxy -3,4,5,6- Tetrahydro -2H- [1,2 '] &lt; / RTI & Epithe 4-carbonyl) - Pyrrolidine -3 days]- methyl - Carbamic acid  4- Fluoro - Phenyl  Ester

rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- (3S, 4R) -4- (4-chloro-phenyl) -pyrrolidine The title compound was prepared in analogy to the procedure described for the synthesis of [(3S, 4R) -methyl-carbamic acid tert- Methyl-carbamic acid 4-fluoro-phenyl ester and 1- (5-hydroxypyridin-2-yl) piperidine-4-carboxylic acid. MS m / e: 553.2 [M + H] &lt; ⁺ &gt;.

Example  321

Acetic acid 4 - {(3R, 4S) -3- (4- Chloro - Phenyl ) -4 - [(4- Fluoro - Phenoxycarbonyl ) - methyl -Amino] - Pyrrolidine Carbonyl} -3,4,5,6- Tetrahydro -2H- [1,2 '] Bipyridinyl -5'-yl ester

[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-hydroxy-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- (Example 320, crude) was treated with acetyl chloride and the mixture was treated with acetonitrile, water, and NEt ₃ &lt; RTI ID = 0.0 &gt; To give the title compound as a pale yellow solid after purification of the product containing fractions by evaporation. MS m / e: 595.4 [M + H] &lt; ⁺ &gt;.

As mentioned previously, the compounds of formula I, and their pharmaceutically usable addition salts, have important pharmaceutical properties. The compounds of the present invention have been identified as antagonists of the neurokinin 3 (NK-3) receptor. The compounds were investigated through the tests given herein below.

Experimental Procedure

The compounds were investigated through the tests given herein below.

[ ³ H] SR142801  Competitive binding assay

^[3 H] SR142801 (product number TRK1035, inactive (specific activity): 74.0 Ci / mmol, UK Buckinghamshire trying meosyam, GE Healthcare materials Care Yu Kay Limited (Amersham, GE Healthcare UK limited) ) and recombinant human NK3 receptor HNK3 receptor binding experiments were performed using membranes isolated from transiently expressing HEK293 cells. After thawing, the membrane cell lysate was centrifuged at 48,000 x g for 10 minutes at 4 ° C and the pellet was resuspended in 50 mM Tris-HCl, 4 mM MnCl ₂ , 1 μM phosphoramidon and 0.1% BSA binding buffer (pH 7.4 ) To create a final assay concentration of 5 [mu] g protein / well. For inhibition experiments, membranes were incubated for 75 min at room temperature with [ ³ H] SR142801 at the same concentration as the K _D value of the radioligand and at 10 concentrations (0.0003-10 μM) of the inhibitory compound (500 μl total reaction volume) Respectively. At the end of the incubation, the membrane was treated with a unit filter (0.3% PEI + 0.3% BSA pre-incubated for 1 hour with GF / C filter with Filtermate 196 Harvester (Packard BioScience, Meriden, Conn. Filtered, 96-well white microplate, Packard Bioscience) and washed four times with ice-cold 50 mM Tris-HCl, pH 7.4 buffer. Non-specific binding to both radioligand was measured in the presence of 10 [mu] M SB222200. 45 [mu] l of MicroSynte 40 (Canberra Packard SA, Zurich, Switzerland) was added and shaken for 1 hour, followed by quenching with a Packard Top-count microplate scintillation counter The radioactivity on the filter was counted (5 min). Inhibit Hill equation curve: y = 100 / (1+ ( x / IC 50) nH) ( wherein, n _H is Excel-foot (Excel-fit) is the slope factor using 4 software (Microsoft)) fitting in accordance with the Respectively. The IC ₅₀ value is derived from the inhibition curve and is calculated by the Cheng-Prussoff equation K _i = IC ₅₀ / (1+ [L] / K _D ), where [L] is the concentration of the radioligand, And K _D is the dissociation constant at the receptor, derived from a saturated isotherm) to calculate the affinity constant (K _i ) value. All experiments were performed twice and K _i The mean ± standard error (SEM) of each value was calculated.

Some results of preferred compounds having hNK-3 receptor affinity of less than 0.10 [mu] M are shown in Table 1 below.

Table 1

The compounds of formula I and their pharmaceutically usable acid addition salts can be used, for example, as medicaments in the form of pharmaceutical preparations. The pharmaceutical preparations can be administered orally, e.g. in the form of tablets, coated tablets, dragees, hard and soft gelatine capsules, solutions, emulsions or suspensions. However, administration can also be effected rectally, e.g., as a suppository, or parenterally, e.g., in the form of an injection.

The compounds of formula I and their pharmaceutically usable acid addition salts can be processed with pharmaceutically inert, inorganic or organic excipients to produce tablets, coated tablets, dragees and hard gelatine capsules. Lactose, corn starch or derivatives thereof, talc, stearic acid or its salts and the like can be used as such excipients for e.g. tablets, dragees and hard gelatine capsules.

Suitable excipients for soft gelatine capsules are, for example, vegetable oils, waxes, fats, semi-solid and liquid polyols and the like.

Suitable excipients for the preparation of solutions and syrups are, for example, water, polyols, saccharose, phosgene and glucose.

Suitable excipients for injection solutions are, for example, water, alcohols, polyols, glycerol, vegetable oils and the like.

Suitable excipients for suppositories are, for example, natural or hardened oils, waxes, fats, semi-solid or liquid polyols and the like.

In addition, the pharmaceutical preparations may contain preservatives, solubilizers, stabilizers, wetting agents, emulsifiers, sweeteners, colorants, flavors, salts for varying the osmotic pressure, buffer solutions, masking agents or antioxidants. It may also contain other pharmacologically important substances.

Dosages can vary within wide limits and can be adjusted according to individual needs in each particular case. Generally, in the case of oral administration, a daily dosage of about 10 to 1000 mg of compound of the formula I per person is appropriate, but may exceed the upper limit if necessary.

Example A

Tablets of the following composition were prepared in a conventional manner:

Example B

Capsules of the following composition were prepared:

First, the active substance, lactose and corn starch were mixed in a grinder followed by a mixer. The mixture was transferred back to the mixer, to which talc was added and mixed thoroughly. The mixture was filled into hard gelatin capsules as a machine.

Example C

Suppositories of the following composition were prepared:

The suppository material was melted in a glass or steel vessel, mixed thoroughly and cooled to 45 캜. Immediately thereafter, fine powdery active substance was added thereto and stirred until completely dispersed. The mixture was poured into a suitably sized suppository mold, allowed to cool and then the suppositories were removed from the mold and individually wrapped with wax paper or metal foil.

Claims (24)

Claims 1. Compounds of the general formula &lt; RTI ID = 0.0 &gt; (I) &lt; / RTI &
(I)

In this formula,
R ¹ is hydrogen, halogen, cyano, C _1-8 alkyl, or C _1-8 alkyl substituted with halogen; n is 1, 2 or 3, provided that when n is 2 or 3, R &lt; ¹ &gt; can be different;
R ² is hydrogen or methyl;
R ³ is (CH ₂ ) _r C (O) NH ₂ or (CH ₂ ) _r -CN where r is 1 or 2, or
The

Aromatic heterocyclic group of formula &lt; RTI ID = 0.0 &gt;
X is N or CH;
Y is ^{-C (R) (R 7)} -, -N (R 7 ') -, -S (O) 2 or O;
R &lt; ⁶ &gt; is hydrogen, di-Ci- _8alkyl or = O;
o and m are independently of each other 0, 1 or 2;
p is 0, 1 or 2;
R is hydrogen, halogen or C _1-8 alkyl;
R ⁷ is hydrogen, halogen, hydroxy, C _1-8 alkyl substituted with hydroxy, cyano, or C _1-8 alkoxy;
R ^{7 '} Hydrogen, -C (O) -C _1-8 alkyl, -C (O) OC _{1-8 alkyl, -C (O) CH 2 OC} 1-8 _{alkyl, -C (O) CH 2 CN} , or
C _3-7 cycloalkyl, C _3-7 cycloalkyl or -CH ₂ -C _3-7 cycloalkyl, wherein said C _3-7 cycloalkyl group is optionally substituted with halogen, C _1-8 alkoxy, C _1-8 alkyl substituted with halogen, cyano, -CH ₂ OC _1-8 alkyl, or C _1-8 alkyl), or
-C (O) -heterocycloalkyl or heterocycloalkyl, or
-C (O) - heteroaryl, or heteroaryl, wherein the heterocycloalkyl or heteroaryl group optionally halogen, C _1-8 alkyl, = O, C _1-8 alkoxy, substituted by halogen, C _1-8 alkyl, C (O) NH-C _1-8 alkyl, C (O) NH ₂ , C (O) -C _1-8 alkyl, S (O) ₂ -C _1-8 alkyl or cyano;
R ⁴ is C _1-8 alkyl, substituted by a C _1-8 alkyl, hydroxy C _1-8 alkyl substituted with halogen, C _1-8 alkyl, optionally substituted with C _3-7 cycloalkyl, (CH _{2) 2 , 3-} OC _1-8 alkyl, CH (CH ₃ ) CH ₂ -OC _1-8 alkyl, (CH ₂ ) _q CN, bicyclo [2.2.1] heptanyl, or
Optionally substituted with C _1-8 alkyl, substituted by halogen, C _1-8 alkyl, C _1-8 alkoxy or halogen (CH _{2) q} -C _3-7 cycloalkyl, or
(CH ₂ ) _q -heterocycloalkyl, (CH ₂ ) _q -C _6-14 aryl, CH (C _1-8 alkyl) -C _6-14 aryl, CH (C _3-7 cycloalkyl) -C _{6- 14} aryl, or (CH ₂ ) _q -heteroaryl, wherein said heterocycloalkyl, C _6-14 aryl or heteroaryl ring is optionally substituted with halogen, C _1-8 alkyl, C _1-8 Alkyl, S (O) ₂ -C _1-8 alkyl, cyano or C _1-8 alkoxy;
q is 0, 1 or 2;
All of said heterocycloalkyl comprises one or more heteroatoms selected from N, O and S and comprises from 3 to 7 ring atoms, wherein all of said heteroaryls contain one or more heteroatoms selected from N, O and S, To 14 ring atoms. The method according to claim 1,
Wherein the compound of formula (I) is a compound of formula (Ia): &lt; EMI ID =
(Ia)

In this formula,
R ¹ is hydrogen, halogen, cyano, C _1-8 alkyl or halogen substituted C _1-8 alkyl; n is 1, 2 or 3, and when n is 2 or 3, R &lt; ¹ &gt; may be different;
R ² is hydrogen or methyl;
R &lt; ⁶ &gt; is hydrogen, di-Ci- _8alkyl or = O;
o and m are independently of each other 0, 1 or 2;
R ^{7 'is} hydrogen, -C (O) -C _1-8 alkyl, -C (O) OC _{1-8 alkyl, -C (O) CH 2 OC} 1-8 alkyl, -C (O) CH ₂ CN , or
C _3-7 cycloalkyl, C _3-7 cycloalkyl or -CH ₂ -C _3-7 cycloalkyl, wherein said C _3-7 cycloalkyl group is optionally substituted with halogen, C _1-8 alkoxy, C _1-8 alkyl substituted with halogen, cyano, -CH ₂ OC _1-8 alkyl or C _1-8 alkyl, or
-C (O) -heterocycloalkyl or heterocycloalkyl, or
-C (O) - heteroaryl, or heteroaryl, wherein the heterocycloalkyl or heteroaryl group optionally halogen, C _1-8 alkyl, = O, C _1-8 alkoxy, substituted by halogen, C _1-8 alkyl, C (O) NH-C _1-8 alkyl, C (O) NH ₂ , C (O) -C _1-8 alkyl, S (O) ₂ -C _1-8 alkyl or cyano;
R ⁴ is C _1-8 alkyl, substituted by a C _1-8 alkyl, hydroxy C _1-8 alkyl substituted with halogen, C _1-8 alkyl, optionally substituted with C _3-7 cycloalkyl, (CH _{2) 2 , 3-} OC _1-8 alkyl, CH (CH ₃ ) CH ₂ -OC _1-8 alkyl, (CH ₂ ) _q CN, bicyclo [2.2.1] heptanyl, or
Optionally substituted with C _1-8 alkyl, substituted by halogen, C _1-8 alkyl, C _1-8 alkoxy or halogen (CH _{2) q} -C _3-7 cycloalkyl, or
(CH ₂ ) _q -heterocycloalkyl, (CH ₂ ) _q -C _6-14 aryl, CH (C _1-8 alkyl) -C _6-14 aryl, CH (C _3-7 cycloalkyl) -C _{6- 14} aryl, or (CH ₂ ) _q -heteroaryl, wherein said heterocycloalkyl, C _6-14 aryl or heteroaryl ring is optionally substituted with halogen, C _1-8 alkyl, C _1-8 Alkyl, S (O) ₂ -C _1-8 alkyl, cyano or C _1-8 alkoxy;
q is 0, 1 or 2;
All of said heterocycloalkyl comprises one or more heteroatoms selected from N, O and S and comprises from 3 to 7 ring atoms, wherein all of said heteroaryls contain one or more heteroatoms selected from N, O and S, To 14 ring atoms. 3. The method of claim 2,
The compound of formula (Ia)
rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- -3-yl} -methyl-carbamic acid tert-butyl ester,
rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- Yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- Yl} -methyl-carbamic acid cyclopentyl ester,
rac- Pyrrolidin-3-yl] -methyl-carbamic acid tert-butyl ester [(3R, 4S) Carbamic acid 4-fluoro-phenyl ester,
[(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- 3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [1- (1- methyl- cyclopropanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
rac - [(3R, 4S) -l- (l-cyclopropylmethyl-piperidine-4-carbonyl) -4- (3,4- dichloro- phenyl) -pyrrolidin- -Carbamic acid phenyl ester,
rac - [(3R, 4S) -l- (l-cyclopropylmethyl-piperidine-4-carbonyl) -4- (3,4- dichloro- phenyl) -pyrrolidin- -Carbamic acid p-tolyl ester,
rac - [(3R, 4S) -l- (l-cyclopropylmethyl-piperidine-4-carbonyl) -4- (3,4- dichloro- phenyl) -pyrrolidin- -Carbamic &lt; / RTI &gt; acid 4-methoxy-phenyl ester,
rac - [(3R, 4S) -l- (l-cyclopropylmethyl-piperidine-4-carbonyl) -4- (3,4- dichloro- phenyl) -pyrrolidin- -Carbamic &lt; / RTI &gt; acid 4-chloro-phenyl ester,
rac - [(3R, 4S) -l- (l-cyclopropylmethyl-piperidine-4-carbonyl) -4- (3,4- dichloro- phenyl) -pyrrolidin- - carbamic acid butyl ester,
rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- Yl} -methyl-carbamic acid 4-chloro-phenyl ester,
rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- Yl} -methyl-carbamic acid phenyl ester,
rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- 3-yl} -methyl-carbamic acid p-tolyl ester,
rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- 3-yl} -methyl-carbamic acid p-methoxyphenyl ester,
[(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- 3-yl} -methyl-carbamic acid p-tolyl ester,
(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [1- (1- methyl- cyclopropanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid p-tolyl ester,
[(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- 3-yl} -methyl-carbamic acid 4-chlorophenyl ester,
(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [1- (1- methyl- cyclopropanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid 4-chlorophenyl ester,
Pyrrolidin-3-yl] -methyl-carbamic acid tert-butyl ester [(3R, 4S) Carbamic acid 4-methoxy-phenyl ester,
4-dichloro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid tert- Carbamic acid 4-methoxy-phenyl ester,
rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- 3-yl} -methyl-carbamic acid 2,2-dimethyl-propyl ester,
rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- Yl} -methyl-carbamic acid prop-2-ynyl ester,
rac- [(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- 3-yl} -methyl-carbamic acid cyclopropylmethyl ester,
rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- Yl} -methyl-carbamic acid 2-cyclopropyl-ethyl ester,
rac - {(3R, 4S) -4- (4-chloro-phenyl) -l- Yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
rac - {(3R, 4S) -4- (4-chloro-phenyl) -l- Yl} -methyl-carbamic acid butyl ester,
rac- [(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- 3-yl} -methyl-carbamic acid 6-chloro-pyridin-3-yl ester,
rac- [(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- 3-yl} -methyl-carbamic acid 3,3,3-trifluoro-propyl ester,
rac- [(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- 3-yl} -methyl-carbamic acid 3,3-dimethyl-butyl ester,
rac- [(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- 3-yl} -methyl-carbamic acid tetrahydro-pyran-4-ylmethyl ester,
rac- [(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- 3-yl} -methyl-carbamic acid cyclopentyl methyl ester,
rac- [(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- 3-yl} -methyl-carbamic acid 3-methyl-oxetan-3-ylmethyl ester,
rac- [(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- 3-yl} -methyl-carbamic acid 6-trifluoromethyl-pyridin-3-yl ester,
[(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- 3-yl} -methyl-carbamic acid 2-cyclopropyl-ethyl ester,
(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [1- (1- methyl- cyclopropanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid 2-cyclopropyl-ethyl ester,
Yl) -pyrrolidin-3-yl &lt; / RTI &gt; } -Methyl-carbamic acid 4-fluoro-phenyl ester,
(3S, 4R) -4- (4-chloro-phenyl) -l- [l- (1- methyl- cyclopropanecarbonyl) -piperidine-4- carbonyll- pyrrolidin- } -Methyl-carbamic acid 4-fluoro-phenyl ester,
rac - {(3R, 4R) -4- (3,4-Dichloro-phenyl) Pyridin-3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
[(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- 3-yl} -methyl-carbamic acid 6-chloro-pyridin-3-yl ester,
(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [1- (1- methyl- cyclopropanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid 6-chloro-pyridin-3-yl ester,
rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- 3-yl} -carbamic acid 4-fluoro-phenyl ester,
rac - {(3R, 4S) -4- (4-Chloro-phenyl) -l- - yl} -methyl-carbamic acid 2-cyclopropyl-ethyl ester,
rac - {(3R, 4S) -4- (4-Chloro-phenyl) -l- -Yl} -methyl-carbamic acid 4-methyl-cyclohexyl ester,
[(3R, 4R) -4- (3,4-Dichloro-phenyl) -l- 3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
(3S, 4S) -4- (3,4-Dichloro-phenyl) -l- 3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
rac - {(3R, 4S) -4- (4-Chloro-phenyl) -l- - yl} -methyl-carbamic acid 2-cyclopropyl-ethyl ester,
rac - {(3R, 4S) -4- (4-Chloro-phenyl) -l- - yl} -methyl-carbamic acid 2-cyclopropyl-ethyl ester,
pyrrolidin-3-yl] -methyl-pyrrolidine-l-carboxylic acid tert-butyl ester as a colorless oil. Carbamic acid 4-fluoro-phenyl ester,
methyl-amino] -pyrrolidine-l- (3S, 4R) -3- (3,4-dichloro-phenyl) -4 - [(4- fluoro-phenoxycarbonyl) Carbonyl} -piperidine-l-carboxylic acid tert-butyl ester,
rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- -3-yl} -methyl-carbamic acid 4,4,4-trifluoro-butyl ester,
[(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- (3R, 4R) -4- (3,4-Dichloro-phenyl) -pyridin-2-yl] Yl) -methyl-carbamic acid (1R, 2S, 4S) - [Lambda] / - Cyclo [2.2.1] hept-2-yl ester,
[(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- 2R, 4S) -bicyclo [2.2.1] hept-2-yl ester and {(3S, 4R) -4- (3,4- Yl) -methyl-carbamic acid (lR, 2R, 4S) - [Lambda] ^^ - Cyclo [2.2.1] hept-2-yl ester,
rac - {(3R, 4S) -4- (3-Chloro-4-methyl-phenyl) Pyridin-3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
rac - {(3R, 4S) -4- (4-chloro-3-methyl-phenyl) Pyridin-3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
rac - [(3R, 4S) -4- (3,4-dichloro-phenyl) -l- (piperidine-4- carbonyl) -pyrrolidin- Phenyl-ester,
rac - [(3R, 4S) -4- (3,4-dichloro-phenyl) -l- (1-propionyl- piperidine- 4- carbonyl) -pyrrolidin- Carbamic acid 4-fluoro-phenyl ester,
rac - [(3R, 4S) -1- (1-cyclopropanecarbonyl-piperidine-4-carbonyl) -4- (3,4- dichloro- phenyl) -pyrrolidin- Methyl-carbamic acid 4-fluoro-phenyl ester,
rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- - yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- [l- (tetrahydro-pyran-4-carbonyl) -piperidine- Pyridin-3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
rac- [(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- [l- (tetrahydro-pyran-4- yl) -piperidine- 4- carbonyl] -pyrrolidin- 3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
rac - [(3R, 4S) -4- (3,4-dichloro-phenyl) -l- -Pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester,
rac - [(3R, 4S) -l- [l- (6-chloro-pyridazin-3- yl) -piperidine-4- carbonyl] -4- (3,4- dichloro- 3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester,
rac - [(3R, 4S) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- , 4-Dichloro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4- fluoro-phenyl ester,
[(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- 3-yl} -methyl-carbamic acid 4,4,4-trifluoro-butyl ester,
(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [1- (1- methyl- cyclopropanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid 4,4,4-trifluoro-butyl ester,
rac- [(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- 3-yl} -methyl-carbamic acid 3,3,4,4,4-pentafluoro-butyl ester,
rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- Yl} -methyl-carbamic acid (S) -l- (tetrahydro-furan-2-yl) methyl ester, and rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- Yl} -methyl-carbamic acid (R) -l- (tetrahydro-furan-2-yl) methyl ester,
rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- Yl} -methyl-carbamic acid (S) -l- (tetrahydro-furan-3-yl) methyl ester, and rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- Yl} -methyl-carbamic acid (R) -l- (tetrahydro-furan-3-yl)
rac- [(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- 3-yl} -methyl-carbamic acid 3,3,3-trifluoro-propyl ester,
rac- [(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- 3-yl} -methyl-carbamic acid 3,3,3-trifluoro-propyl ester,
rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- -3-yl} -methyl-carbamic acid 4,4,5,5,5-pentafluoro-pentyl ester,
rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- Yl} -methyl-carbamic acid 1-methyl-cyclopropylmethyl ester,
rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- Yl} -methyl-carbamic acid 2-methyl-cyclopropylmethyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester,
rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- Yl} -methyl-carbamic acid 4-fluoro-benzyl ester,
rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- Yl} -methyl-carbamic acid 3-hydroxy-3-methyl-butyl ester,
rac [(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- 3-yl} -methyl-carbamic acid 4,4-difluoro-cyclohexylmethyl ester,
Yl) -pyrrolidin-3-yl &lt; / RTI &gt; } -Methyl-carbamic acid 4,4,4-trifluoro-butyl ester,
(3S, 4R) -4- (4-chloro-phenyl) -l- [l- (1- methyl- cyclopropanecarbonyl) -piperidine-4- carbonyll- pyrrolidin- } -Methyl-carbamic acid 4,4,4-trifluoro-butyl ester,
rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- 3-yl} -methyl-carbamic acid 4,4-difluoro-cyclohexyl ester,
rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- 3-yl} -methyl-carbamic acid 4-trifluoromethyl-cyclohexyl ester,
(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [1- (1- methyl- cyclopropanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid l-methyl-cyclopropylmethyl ester,
[(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- 3-yl} -methyl-carbamic acid l-methyl-cyclopropylmethyl ester,
[(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- 3-yl} -methyl-carbamic acid 4-trifluoromethyl-cyclohexyl ester,
(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [1- (1- methyl- cyclopropanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid 4-trifluoromethyl-cyclohexyl ester,
{(3S, 4R) -4- (4-Chloro-phenyl) -l- [l- ⁶ -Piperidin-4-carbonyl] -pyrrolidin-3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
[(3S, 4R) -4- (4-Chloro-phenyl) -l- - yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
rac - {(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- 3-yl} -methyl-carbamic acid 3,3-difluoro-cyclopentylmethyl ester,
Yl) -piperidine-4-carbonyl] -pyrrolidin-3-yl} - (3S, 4R) } -Methyl-carbamic acid 4-fluoro-phenyl ester,
(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [1- (1- methyl- cyclopropanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid 3-bromo-4-fluoro-phenyl ester,
{(3S, 4R) -4- (4-Chloro-phenyl) -1- [1- (1,1- dioxo-tetrahydro- ⁶ -Piperidin-4-carbonyl] -pyrrolidin-3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
Pyridin-3-yl) -piperidine-4-carbonyl] -pyrrolidin-3 (2S) - yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid tert-butyl ester,
rac - [(3S, 4R) -1- (5'-tert-butylcarbamoyl-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- 4-chloro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester,
rac - [(3S, 4R) -1- (5'-tert-butylcarbamoyl-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- 4-Chloro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4- trifluoromethyl- cyclohexyl ester,
[(3R, 4S) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester,
[(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [l- (tetrahydro- pyran- 4- yl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid 4-trifluoromethyl-cyclohexyl ester,
rac - [(3S, 4R) -1- (5'-tert-butylcarbamoyl-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- 3-yl] -methyl-carbamic acid 4,4,4-trifluoro-butyl ester, 4- (4-chloro-phenyl) -pyrrolidin-
[(3R, 4S) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-trifluoromethyl-cyclohexyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-trifluoromethyl-cyclohexyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4,4,4-trifluoro-butyl ester,
[(3R, 4S) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4,4,4-trifluoro-butyl ester,
[(3S, 4R) -4- (4-fluoro-phenyl) -l- Yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
Piperidin-4-carbonyl] -pyrrolidine-3-carboxylic acid {(3R, 4S) Yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
[(3S, 4R) -1- (5'-Cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- Fluoro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester,
[(3R, 4S) -1- (5'-Cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- Fluoro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester,
Methyl-amino] -pyrrolidine-l-carbonyl} - piperidine-l-carboxylic acid ethyl ester was prepared from 4 - {(3R, 4S) 1-carboxylic acid tert-butyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -l- Yl] -pyrrolidin-3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -l- (piperidine- 4- carboyl) -pyrrolidin-3- yl] -methyl- carbamic acid 4-fluoro-phenyl ester ,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid ethyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid isopropyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid propyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid isobutyl ester,
Pyridin-3-yl) -piperidine-4-carbonyl] -pyrrolidine-l- 3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
(3S, 4R) -4- (4-chloro-phenyl) -l- [l- (1- methyl- cyclopropanecarbonyl) -piperidine-4- carbonyll- pyrrolidin- } -Methyl-carbamic acid isobutyl ester,
(3S, 4R) -4- (4-chloro-phenyl) -l- [l- (1- methyl- cyclopropanecarbonyl) -piperidine-4- carbonyll- pyrrolidin- } -Methyl-carbamic acid propyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid cyclohexyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 3,3,3-trifluoro-propyl ester,
[(3R, 4S) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 3,3,3-trifluoro-propyl ester,
Pyrrolidin-3-yl] -methyl-carbamic acid 4- (4-fluoro-phenyl) Fluoro-phenyl ester,
Methyl-amino] -pyrrolidine-l-carbonyl} - &lt; / RTI &gt; L-carboxylic acid tert-butyl ester, &lt; RTI ID = 0.0 &gt;
(3S, 4R) -4- (4-chloro-phenyl) -l- [l- (1- methyl- cyclopropanecarbonyl) -piperidine-4- carbonyll- pyrrolidin- } -Methyl-carbamic acid cyclohexyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid l-cyclopropyl-ethyl ester,
(3S, 4R) -4- (4-chloro-phenyl) -l- [l- (1- methyl- cyclopropanecarbonyl) -piperidine-4- carbonyll- pyrrolidin- } -Methyl-carbamic acid 1-cyclopropyl-ethyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid oxetan-3-yl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid tetrahydro-pyran-4-yl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid tert-butyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 2,2,2-trifluoro-ethyl ester,
[(3S, 4R) -1- (5'-Cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- Dichloro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-trifluoromethyl-cyclohexyl ester,
[(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- Pyridin-3-yl} -methyl-carbamic acid 4-trifluoromethyl-cyclohexyl ester,
(3S, 4R) -4- (4-chloro-phenyl) -l- [l- (1- methyl- cyclopropanecarbonyl) -piperidine-4- carbonyll- pyrrolidin- } -Methyl-carbamic acid tetrahydro-pyran-4-yl ester,
(3S, 4R) -4- (4-chloro-phenyl) -l- [l- (1- methyl- cyclopropanecarbonyl) -piperidine-4- carbonyll- pyrrolidin- } -Methyl-carbamic acid tert-butyl ester,
(3S, 4R) -4- (4-chloro-phenyl) -l- [l- (1- methyl- cyclopropanecarbonyl) -piperidine-4- carbonyll- pyrrolidin- } -Methyl-carbamic acid 2,2,2-trifluoroethyl ester,
(3S, 4R) -4- (4-chloro-phenyl) -l- [l- (1- methyl- cyclopropanecarbonyl) -piperidine-4- carbonyll- pyrrolidin- } -Methyl-carbamic acid 2,2,2-trifluoro-l-methyl-ethyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 2,2,2-trifluoro-l-methyl-ethyl ester,
Yl) -piperidine-4-carbonyl] -pyrrolidin-3 (1 H) -quinolin- - yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -l- (pyrrolidine- 3- carbonyl) -pyrrolidin-3- yl] -methyl- carbamic acid 4- fluoro-phenyl ester ,
Yl) -piperidine-4-carbonyl] -pyrrolidine-1-carboxylic acid tert-butyl ester {(3S, 4R) 3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
Pyrrolidin-3-yl] -methyl-carbamic acid 4- (4-fluoro-phenyl) Fluoro-phenyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -l- (1- cyclopropanecarbonyl- pyrrolidine- 3- carbonyl) -pyrrolidin-3- yl] -methyl- carbamic acid 4-fluoro-phenyl ester,
Pyrrolidine-3-carbonyl] -pyrrolidin-3-yl} - (2-methoxy- Methyl-carbamic acid 4-fluoro-phenyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid cyclobutyl ester,
(3S, 4R) -4- (4-chloro-phenyl) -l- [l- (1- methyl- cyclopropanecarbonyl) -piperidine-4- carbonyll- pyrrolidin- } -Methyl-carbamic acid cyclobutyl ester,
(3S, 4R) -4- (4-chloro-phenyl) -l- [l- (1- methyl- cyclopropanecarbonyl) -piperidine-4- carbonyll- pyrrolidin- } -Methyl-carbamic acid 2,2,3,3-tetrafluorocyclobutyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 2,2,3,3-tetrafluorocyclobutyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 3,3,3-trifluoro-l-methyl-propyl ester,
(3S, 4R) -4- (4-chloro-phenyl) -l- [l- (1- methyl- cyclopropanecarbonyl) -piperidine-4- carbonyll- pyrrolidin- } -Methyl-carbamic acid 3,3,3-trifluoro-l-methyl-propyl ester,
Yl) -pyrrolidine-3-carbonyl] -pyrrolidin-3-yl} - (3- } -Methyl-carbamic acid 4-fluoro-phenyl ester,
[(3S, 4R) -4- (4-Chloro-phenyl) -1- (5'-methanesulfonyl-3,4,5,6-tetrahydro- 4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -l- (5 ' -trifluoromethyl-3,4,5,6-tetrahydro- Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester,
[(3S, 4R) -1- (5'-Acetyl-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester,
Yl] -piperidin-4-carbonyl) -pyrrolidin-3-yl] -methyl- Carbamic acid 4-fluoro-phenyl ester,
Pyrrolidine-4-carbonyl] -pyrrolidin-3-one To a solution of {(3S, 4R) -4- - yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (4'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (3'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester,
Yl) -piperidine-4-carbonyl] -pyrrolidin-3 (2S) - yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -l- (3 ' -chloro-5 ' -trifluoromethyl-3,4,5,6-tetrahydro- -] bipyridinyl-4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4- fluoro-phenyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (6'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester,
[(3S, 4R) -4- (4-Chloro-phenyl) -l- 3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
Yl] -piperidin-4-carbonyl) -pyrrolidin-3-yl] -methyl- Carbamic acid 4-fluoro-phenyl ester,
[(3S, 4R) -4- (4-Chloro-phenyl) -l- 3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
Yl) -piperidine-4-carbonyl] -pyrrolidin-3 (2S) -4- [ - yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -l- (5'-methyl-3,4,5,6-tetrahydro- Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-fluoro-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester,
[(3S, 4R) -1- (5'-Carbamoyl-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- Chloro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester,
Pyridin-3-yl) -piperidine-4-carbonyl] -pyrrolidine-l- 3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (6'-cyano-3,4,5,6-tetrahydro-2H- [1,3 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -l- (5'-chloro-3,4,5,6-tetrahydro- Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid phenyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-methoxy-phenyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid p-tolyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-chloro-phenyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid cyclopentyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 2,2-dimethyl-propyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 2-methoxy-ethyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-trifluoromethyl-phenyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 2,4-difluoro-phenyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 3,4-difluoro-phenyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (6'-cyano-3,4,5,6-tetrahydro-2H- [1,3 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 3,5-difluoro-phenyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 2,3-difluoro-phenyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 2-fluoro-phenyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 2-chloro-phenyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 3-fluoro-propyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid cyclopropylmethyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 3-methoxy-propyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 1-methyl-cyclopropylmethyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 3-methyl-oxetan-3-ylmethyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 2-cyclopropyl-ethyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-methyl-cyclohexyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-methyl-cyclohexyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 2-methoxy-1-methyl-ethyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 2-fluoro-ethyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4- methanesulfonyl-phenyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 3-cyano-phenyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid l- (4-fluoro-phenyl)
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 2-fluoro-l-fluoromethyl-ethyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-cyano-phenyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid o-tolyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid m-tolyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid tetrahydro-pyran-4-ylmethyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid tetrahydro-furan-2-ylmethyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid tetrahydro-furan-3-ylmethyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 1,1-dimethyl-propyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 2,2,2-trifluoro-1,1-dimethyl- ethyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbamoyl) -pyrrolidin-3-yl] -methyl-carbamic acid l- (4-fluoro-phenyl) -propyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-cyano-2-fluoro-phenyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-methoxy-cyclohexyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid cyclopropyl- (4-fluoro-phenyl)
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-methyl-l-trifluoromethyl- cyclohexyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 1,4-dimethyl-cyclohexyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 1,4-dimethyl-cyclohexyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- - carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid l-methyl-cyclopentyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 5-chloro-pyridin-2-
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-cyano-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-cyano-3-fluoro-phenyl ester,
4-carbonyl) -4- (4-chloro-phenyl) -pyrrolidin-3- yl] -methyl-carbamic acid 4- fluoro Phenyl-ester,
4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid &lt; / RTI &gt; 4-fluoro-phenyl ester,
[(3S, 4R) -4- (4-Chloro-phenyl) -l- 3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -l- [l- (3- fluoro-cyclobutanecarbonyl) -piperidine- 4- carbonyl] -pyrrolidin- Yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -l- [l- (3,3- difluoro-cyclobutanecarbonyl) -piperidine-4- carbonyl] -pyrrolidine Yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
(3S, 4R) -4- (4-chloro-phenyl) -l- [l- (3- methoxy- cyclobutanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- Yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
[(3S, 4R) -4- (4-Chloro-phenyl) -l- [1- (1- trifluoromethyl- cyclobutanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
4-carbonyl] -pyrrolidin-3-yl} - (2-cyano-acetyl) -piperidine- Methyl-carbamic acid 4-fluoro-phenyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -l- [1- (1- cyano- cyclopropanecarbonyl) -piperidine- 4- carbonyl] -pyrrolidin- Yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
[(3S, 4R) -4- (4-Chloro-phenyl) -l- l- (l- trifluoromethyl- cyclopropanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
{(3S, 4R) -4- (4-Chloro-phenyl) -l- [l- (2,2- difluoro- cyclopropanecarbonyl) -piperidine- 4- carbonyl] -pyrrolidine Yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -l- [l- (tetrahydro-pyran-4-carbonyl) -piperidine- 4- carbonyl] -pyrrolidin- Yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
4- (4-chloro-phenyl) -l- [l- (2,2-dimethyl-tetrahydro-pyran-4-carbonyl) -piperidine- -Pyrrolidin-3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -l- [l- (1- methoxymethyl- cyclopropanecarbonyl) -piperidine-4- carbonyl] -pyrrolidin- - yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -l- [l- (2,2- dimethyl- cyclopropanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
[(3S, 4R) -4- (4-Chloro-phenyl) -l- [1- (5- trifluoromethyl- pyridine- 2- carbonyl) -piperidine-4- carbonyl] -pyrrole Pyridin-3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
Pyridin-2-carbonyl) -piperidine-4-carbonyl] -pyrrolidine-l- 3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
{(3S, 4R) -4- (4-Chloro-phenyl) -l- Yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
[(3S, 4R) -4- (4-Chloro-phenyl) -l- [1- (1-isopropyl-6-oxo-piperidine- 3- carbonyl) -piperidine- ] -Pyrrolidin-3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
- [(3S, 4R) -1- (1-cyclobutanecarbonyl-piperidine-4- carbonyl) -4- (3,4- dichloro- phenyl) -pyrrolidin- -Carbamic &lt; / RTI &gt; acid 4-fluoro-phenyl ester,
[(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- 3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [l- (3- fluoro-cyclobutanecarbonyl) -piperidine-4- carbonyl] -pyrrolidine Yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
- (3,3-difluoro-cyclobutanecarbonyl) -piperidine-4-carbonyl] - Pyrrolidin-3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [l- (3- methoxy- cyclobutanecarbonyl) -piperidine-4- carbonyl] -pyrrolidine Yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
[(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- 3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
[(3S, 4R) -1- [1- (2-cyano-acetyl) -piperidine-4- carbonyl] -4- (3,4- dichloro- phenyl) -pyrrolidin- Yl-methyl-carbamic acid 4-fluoro-phenyl ester,
[(3S, 4R) -1- [1- (1 -cyano-cyclopropanecarbonyl) -piperidine-4- carbonyl] -4- (3,4- dichloro- phenyl) -pyrrolidine Yl] -methyl-carbamic acid 4-fluoro-phenyl ester,
[(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- 3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
[(3S, 4R) -4- (3,4-Dichloro-phenyl) -1- [1- (2,2- difluoro- cyclopropanecarbonyl) -piperidine- Pyrrolidin-3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [l- (tetrahydro-pyran- Yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
4- (3,4-Dichloro-phenyl) -l- [l- (2,2-dimethyl-tetrahydro-pyran-4-carbonyl) -piperidin- Carbonyl] -pyrrolidin-3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [l- (1- methoxymethyl- cyclopropanecarbonyl) -piperidine-4- carbonyl] -pyrrole Pyridin-3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
[(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [l- (2,2- dimethyl- cyclopropanecarbonyl) -piperidine- 3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
[(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- -Pyrrolidin-3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
[(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- 3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
[(3S, 4R) -4- (3,4-Dichloro-phenyl) -1- [1- (6-oxo-piperidine- Pyrrolidin-3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
- (l-isopropyl-6-oxo-piperidine-3-carbonyl) -piperidin-4 - carbonyl] -pyrrolidin-3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
4- [(3,4-dichloro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester,
4-carbonyl] -4- (4-fluoro-phenyl) -pyrrolidin-3-yl] -Methyl-carbamic acid 4-fluoro-phenyl ester,
4-carbonyl) -4- (4-fluoro-phenyl) -pyrrolidin-3- yl] -methyl- carbamic acid 4- Fluoro-phenyl ester,
[(3S, 4R) -4- (4-fluoro-phenyl) -l- Yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
4- [4- (4-fluoro-phenyl) -pyrrolidin-3-yl] -Yl] -methyl-carbamic acid 4-fluoro-phenyl ester,
4- [4- (4-fluoro-phenyl) -pyrrolidin-3-yl] -Yl] -methyl-carbamic acid 4-fluoro-phenyl ester,
[(3S, 4R) -4- (4-fluoro-phenyl) -l- [1- (1- trifluoromethyl- cyclobutanecarbonyl) -piperidine-4- carbonyl] -pyrrolidine Yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
[(3S, 4R) -4- (4-fluoro-phenyl) -l- 3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
{(3S, 4R) -4- (4-fluoro-phenyl) -1- [1- (6-oxo- piperidine-3- carbonyl) -piperidine-4- carbonyl] Pyridin-3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
[(3S, 4R) -4- (3,4-Dichloro-phenyl) -1- [1 - ((S) -4-oxo-azetidine- Yl] -pyrrolidin-3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [1- (1- methyl- cyclopropanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid 2-fluoro-pyridin-3-yl ester,
(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [1- (1- methyl- cyclopropanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid 2,6-dimethyl-pyridin-4-yl ester,
(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [1- (1- methyl- cyclopropanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid pyridin-3-yl ester,
(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [1- (1- methyl- cyclopropanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid 6-methyl-pyridin-3-yl ester,
(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [1- (1- methyl- cyclopropanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid pyridin-4-yl ester,
(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [1- (1- methyl- cyclopropanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid 2,6-dimethyl-pyridin-3-yl ester,
(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [1- (1- methyl- cyclopropanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid 5-fluoro-pyridin-3-yl ester,
(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [1- (1- methyl- cyclopropanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid 6-chloro-pyridin-2-yl ester,
(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [1- (1- methyl- cyclopropanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid 2-chloro-5-fluoro-pyridin-3-
(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [1- (1- methyl- cyclopropanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid 2-chloro-pyridin-3-yl ester,
(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [1- (1- methyl- cyclopropanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid 6-trifluoromethyl-pyridin-3-yl ester,
(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [1- (1- methyl- cyclopropanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid 2-cyano-pyridin-3-yl ester,
(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- [1- (1- methyl- cyclopropanecarbonyl) -piperidine- 4- carbonyll- pyrrolidin- 3-yl} -methyl-carbamic acid 2-fluoro-6-methyl-pyridin-3-
[(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- (5 ' -trifluoromethyl-3,4,5,6-tetrahydro- 4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester,
[(3S, 4R) -1- (5'-Acetyl-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl-4-carbonyl) -4- -Dichloro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester,
[(3S, 4R) -1- (5'-Chloro-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl-4-carbonyl) -4- -Dichloro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester,
[(3S, 4R) -4- (3,4-Dichloro-phenyl) -1- (5'-fluoro-3,4,5,6-tetrahydro-2H- [ Yl-4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester,
[(3S, 4R) -1- (5'-Carbamoyl-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- Dichloro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester,
Fluoro-3,4,5,6-tetrahydro-2H- [1,2 &apos;] - 4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester,
[(3S, 4R) -4- (4-chloro-3-fluoro-phenyl) Pyridin-4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4- fluoro-phenyl ester,
[(3S, 4R) -4- (4-chloro-3-fluoro-phenyl) -l- (5 ' -trifluoromethyl-3,4,5,6-tetrahydro- -] bipyridinyl-4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4- fluoro-phenyl ester,
[(3S, 4R) -1- (5'-Acetyl-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -3-fluoro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4- fluoro-phenyl ester,
[(3S, 4R) -4- (3-Chloro-4-fluoro-phenyl) 4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester,
[(3S, 4R) -4- (3-Chloro-4-fluoro-phenyl) -l- (5'-chloro-3,4,5,6-tetrahydro- Pyridin-4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4- fluoro-phenyl ester,
[(3S, 4R) -4- (3-Chloro-4-fluoro-phenyl) -l- (5 ' -trifluoromethyl-3,4,5,6-tetrahydro- -] bipyridinyl-4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4- fluoro-phenyl ester,
[(3S, 4R) -1- (5'-Acetyl-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -4-fluoro-phenyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4- fluoro-phenyl ester,
- (S) -4-oxo-azetidine-2-carbonyl) -piperidine-4-carbonyl] - Pyrrolidin-3-yl} -methyl-carbamic acid 4-fluoro-phenyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -1- (5'-hydroxy-3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl- -Carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester, or
Methyl-amino] -pyrrolidine-1-carbonyl} - (4-chloro-phenyl) -4 - [(4- fluoro-phenoxycarbonyl) 3,4,5,6-tetrahydro-2H- [1,2 '] bipyridinyl-5'-yl ester. The method according to claim 1,
Wherein the compound of formula (I) is a compound of formula (Ib): or a pharmaceutically acceptable salt thereof:
(Ib)

In this formula,
R ¹ is hydrogen, halogen, cyano, C _1-8 alkyl or halogen substituted C _1-8 alkyl; n is 1, 2 or 3, and when n is 2 or 3, R &lt; ¹ &gt; may be different;
R ² is hydrogen or methyl;
R &lt; ⁶ &gt; is hydrogen, di-Ci- _8alkyl or = O;
o and m are independently of each other 0, 1 or 2;
R is hydrogen, halogen, or _C1-8 alkyl;
R ⁷ is hydrogen, halogen, hydroxy, C _1-8 alkyl substituted with hydroxy, cyano, or C _1-8 alkoxy;
R ⁴ is C _1-8 alkyl, substituted by a C _1-8 alkyl, hydroxy C _1-8 alkyl substituted with halogen, C _1-8 alkyl, optionally substituted with C _3-7 cycloalkyl, (CH _{2) 2 , 3-} OC _1-8 alkyl, CH (CH ₃ ) CH ₂ -OC _1-8 alkyl, (CH ₂ ) _q CN, bicyclo [2.2.1] heptanyl, or
Optionally substituted with C _1-8 alkyl, substituted by halogen, C _1-8 alkyl, C _1-8 alkoxy or halogen (CH _{2) q} -C _3-7 cycloalkyl, or
(CH ₂ ) _q -heterocycloalkyl, (CH ₂ ) _q -C _6-14 aryl, CH (C _1-8 alkyl) -C _6-14 aryl, CH (C _3-7 cycloalkyl) -C _{6- 14} aryl, or (CH ₂ ) _q -heteroaryl, wherein said heterocycloalkyl, C _6-14 aryl or heteroaryl ring is optionally substituted with halogen, C _1-8 alkyl, C _1-8 Alkyl, S (O) ₂ -C _1-8 alkyl, cyano or C _1-8 alkoxy;
q is 0, 1 or 2;
Wherein said heterocycloalkyl comprises at least one heteroatom selected from N, O and S and comprises from 3 to 7 ring atoms, said heteroaryl comprising at least one heteroatom selected from N, O and S and having from 5 to 14 Ring atoms. 5. The method of claim 4,
The compound of formula (Ib)
[(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- (trans-4-hydroxy- cyclohexanecarbonyl) -pyrrolidin-3- yl] -methyl- carbamic acid 4 - fluoro-phenyl ester,
[(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- (trans-4-hydroxy-cyclohexanecarbonyl) -pyrrolidin- - fluoro-phenyl ester,
(cis-4-hydroxy-cyclohexanecarbonyl) -pyrrolidin-3-yl] -methyl-carbaldehyde 4-fluoro-phenyl ester,
yl) -methyl-carbaldehyde &lt; RTI ID = 0.0 &gt; (3-methoxy-phenyl) 4-fluoro-phenyl ester,
(trans-4-hydroxy-4-methyl-cyclohexanecarbonyl) -pyrrolidin-3-yl] -Methyl-carbamic acid 4-fluoro-phenyl ester,
(cis-4-hydroxy-4-methyl-cyclohexanecarbonyl) -pyrrolidin-3-yl] -Methyl-carbamic acid 4-fluoro-phenyl ester,
- [(3R, 4S) -4- (3,4-Dichloro-phenyl) -l- (cis-4-hydroxy- cyclohexanecarbonyl) -pyrrolidin- - fluoro-phenyl ester,
[(3S, 4R) -4- (3,4-Dichloro-phenyl) -l- (cis-4-hydroxy- cyclohexanecarbonyl) -pyrrolidin- - fluoro-phenyl ester,
Pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl} -piperidine-l- Esther,
[(3S, 4R) -4- (4-chloro-phenyl) -l- (4-cyano- cyclohexanecarbonyl) -pyrrolidin-3- yl] -methyl- carbamic acid 4- Esther,
[(3S, 4R) -4- (4-chloro-phenyl) -l- (4- hydroxymethyl- cyclohexanecarbonyl) -pyrrolidin-3- yl] -methyl- carbamic acid 4- Phenyl ester,
[(3S, 4R) -4- (4-chloro-phenyl) -l- (4,4- difluoro- cyclohexanecarbonyl) -pyrrolidin- 3-yl] -methyl- carbamic acid 4- Phenyl-ester, or
Pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl} -piperidine-l- Ester. The method according to claim 1,
Wherein the compound of formula (I) is a compound of formula (Ic): or a pharmaceutically acceptable salt thereof:
(Ic)

In this formula,
R ¹ is hydrogen, halogen, cyano, C _1-8 alkyl or halogen substituted C _1-8 alkyl; n is 1, 2 or 3, and when n is 2 or 3, R &lt; ¹ &gt; may be different;
R ² is hydrogen or methyl;
p is 0, 1 or 2;
R ⁴ is C _1-8 alkyl, substituted by a C _1-8 alkyl, hydroxy C _1-8 alkyl substituted with halogen, C _1-8 alkyl, optionally substituted with C _3-7 cycloalkyl, (CH _{2) 2 , 3-} OC _1-8 alkyl, CH (CH ₃ ) CH ₂ -OC _1-8 alkyl, (CH ₂ ) _q CN, bicyclo [2.2.1] heptanyl,
Optionally substituted with C _1-8 alkyl, substituted by halogen, C _1-8 alkyl, C _1-8 alkoxy or halogen (CH _{2) q} -C _3-7 cycloalkyl, or
(CH ₂ ) _q -heterocycloalkyl, (CH ₂ ) _q -C _6-14 aryl, CH (C _1-8 alkyl) -C _6-14 aryl, CH (C _3-7 cycloalkyl) -C _{6- 14} aryl, or (CH ₂ ) _q -heteroaryl, wherein said heterocycloalkyl, C _6-14 aryl or heteroaryl ring is optionally substituted with halogen, C _1-8 alkyl, C _1-8 Alkyl, S (O) ₂ -C _1-8 alkyl, cyano or C _1-8 alkoxy;
q is 0, 1 or 2;
Wherein said heterocycloalkyl comprises at least one heteroatom selected from N, O and S and comprises from 3 to 7 ring atoms, said heteroaryl comprising at least one heteroatom selected from N, O and S and having from 5 to 14 Ring atoms. The method according to claim 6,
The compound of formula (Ic)
(morpholine-4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro Phenyl-ester, or
- [(3S, 4R) -4- (4-chloro-phenyl) -l- (3- morpholin- 4- yl- propionyl) -pyrrolidin- 3- yl] -methyl- carbamic acid 4- fluoro - &lt; / RTI &gt; phenyl ester. The method according to claim 1,
Wherein the compound of formula (I) is a compound of formula (Id): &lt; EMI ID =
(Id)

In this formula,
R ¹ is hydrogen, halogen, cyano, C _1-8 alkyl or halogen substituted C _1-8 alkyl; n is 1, 2 or 3, and when n is 2 or 3, R &lt; ¹ &gt; may be different;
R ² is hydrogen or methyl;
R &lt; ⁶ &gt; is hydrogen, di-Ci- _8alkyl or = O;
o and m are independently of each other 0, 1 or 2;
R ⁴ is C _1-8 alkyl, substituted by a C _1-8 alkyl, hydroxy C _1-8 alkyl substituted with halogen, C _1-8 alkyl, optionally substituted with C _3-7 cycloalkyl, (CH _{2) 2 , 3-} OC _1-8 alkyl, CH (CH ₃ ) CH ₂ -OC _1-8 alkyl, (CH ₂ ) _q CN, bicyclo [2.2.1] heptanyl, or
Optionally substituted with C _1-8 alkyl, substituted by halogen, C _1-8 alkyl, C _1-8 alkoxy or halogen (CH _{2) q} -C _3-7 cycloalkyl, or
(CH ₂ ) _q -heterocycloalkyl, (CH ₂ ) _q -C _6-14 aryl, CH (C _1-8 alkyl) -C _6-14 aryl, CH (C _3-7 cycloalkyl) -C _{6- 14} aryl, or (CH ₂ ) _q -heteroaryl, wherein said heterocycloalkyl, C _6-14 aryl or heteroaryl ring is optionally substituted with halogen, C _1-8 alkyl, C _1-8 Alkyl, S (O) ₂ -C _1-8 alkyl, cyano or C _1-8 alkoxy;
q is 0, 1 or 2;
Wherein said heterocycloalkyl comprises at least one heteroatom selected from N, O and S and comprises from 3 to 7 ring atoms, said heteroaryl comprising at least one heteroatom selected from N, O and S and having from 5 to 14 Ring atoms. 9. The method of claim 8,
The compound of formula (Id)
4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid 4 &lt; RTI ID = 0.0 &gt; - fluoro-phenyl ester,
Pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-4-fluoro-4- Phenyl-ester,
[(3S, 4R) -4- (3,4-Dichloro-phenyl) - l- (tetrahydro-pyran- Phenyl-ester,
Pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl (2-methyl- Esther,
4-carbonyl) -pyrrolidin-3-yl] -methyl-carbamic acid tert-butyl ester was prepared in analogy to the procedure described for the synthesis of [(3S, 4R) -4- 4-fluoro-phenyl ester,
Pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl) -phenyl] - Esther,
Pyrrolidin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl} -pyrrolidine The title compound was prepared in analogy to the procedure described for the synthesis of [(3S, 4R) -4- Ester, or
Pyrrolidin-3-yl] -methyl-carbamic acid 4-tricyclo [6.3.1.0 &lt; 2 &gt; Fluoromethyl-cyclohexyl ester. &Lt; / RTI &gt; The method according to claim 1,
Wherein the compound of formula I is a compound of formula &lt; RTI ID = 0.0 &gt; (Ie) &lt; / RTI &
(Ie)

In this formula,
R ¹ is hydrogen, halogen, cyano, C _1-8 alkyl or halogen substituted C _1-8 alkyl; n is 1, 2 or 3, and when n is 2 or 3, R &lt; ¹ &gt; may be different;
R ² is hydrogen or methyl;
R ⁴ is C _1-8 alkyl, substituted by a C _1-8 alkyl, hydroxy C _1-8 alkyl substituted with halogen, C _1-8 alkyl, optionally substituted with C _3-7 cycloalkyl, (CH _{2) 2 , 3-} OC _1-8 alkyl, CH (CH ₃ ) CH ₂ -OC _1-8 alkyl, (CH ₂ ) _q CN, bicyclo [2.2.1] heptanyl, or
Optionally substituted with C _1-8 alkyl, substituted by halogen, C _1-8 alkyl, C _1-8 alkoxy or halogen (CH _{2) q} -C _3-7 cycloalkyl, or
(CH ₂ ) _q -heterocycloalkyl, (CH ₂ ) _q -C _6-14 aryl, CH (C _1-8 alkyl) -C _6-14 aryl, CH (C _3-7 cycloalkyl) -C _{6- 14} aryl, or (CH ₂ ) _q -heteroaryl, wherein said heterocycloalkyl, C _6-14 aryl or heteroaryl ring is optionally substituted with halogen, C _1-8 alkyl, C _1-8 Alkyl, S (O) ₂ -C _1-8 alkyl, cyano or C _1-8 alkoxy;
q is 0, 1 or 2;
Wherein said heterocycloalkyl comprises at least one heteroatom selected from N, O and S and comprises from 3 to 7 ring atoms, said heteroaryl comprising at least one heteroatom selected from N, O and S and having from 5 to 14 Ring atoms. 11. The method of claim 10,
The compound of formula (Ie) is reacted with rac - [(3R, 4S) -1- (3-carbamoyl-propionyl) -4- (3,4- dichloro- phenyl) -pyrrolidin- -Carbamic &lt; / RTI &gt; acid 4-fluoro-phenyl ester. The method according to claim 1,
Wherein the compound of formula (I) is a compound of formula (I): &lt; EMI ID =
(If)

In this formula,
R ¹ is hydrogen, halogen, cyano, C _1-8 alkyl or halogen substituted C _1-8 alkyl; n is 1, 2 or 3, and when n is 2 or 3, R &lt; ¹ &gt; may be different;
R ² is hydrogen or methyl;
R &lt; ⁶ &gt; is hydrogen, di-Ci- _8alkyl or = O;
o and m are independently of each other 0, 1 or 2;
R ⁴ is C _1-8 alkyl, substituted by a C _1-8 alkyl, hydroxy C _1-8 alkyl substituted with halogen, C _1-8 alkyl, optionally substituted with C _3-7 cycloalkyl, (CH _{2) 2 , 3-} OC _1-8 alkyl, CH (CH ₃ ) CH ₂ -OC _1-8 alkyl, (CH ₂ ) _q CN, bicyclo [2.2.1] heptanyl, or
Optionally substituted with C _1-8 alkyl, substituted by halogen, C _1-8 alkyl, C _1-8 alkoxy or halogen (CH _{2) q} -C _3-7 cycloalkyl, or
(CH ₂ ) _q -heterocycloalkyl, (CH ₂ ) _q -C _6-14 aryl, CH (C _1-8 alkyl) -C _6-14 aryl, CH (C _3-7 cycloalkyl) -C _{6- 14} aryl, or (CH ₂ ) _q -heteroaryl, wherein said heterocycloalkyl, C _6-14 aryl or heteroaryl ring is optionally substituted with halogen, C _1-8 alkyl, C _1-8 Alkyl, S (O) ₂ -C _1-8 alkyl, cyano or C _1-8 alkoxy;
q is 0, 1 or 2;
Wherein said heterocycloalkyl comprises at least one heteroatom selected from N, O and S and comprises from 3 to 7 ring atoms, said heteroaryl comprising at least one heteroatom selected from N, O and S and having from 5 to 14 Ring atoms. The method according to claim 1,
Wherein the compound of formula I is selected from the group consisting of [(3R, 4S) -4- (3,4-dichloro-phenyl) Methyl-carbamic acid 4-fluoro-phenyl ester. The method according to claim 1,
Wherein the compound of formula I is a compound of formula Ig: &lt; EMI ID =
[Chemical Formula Ig]

In this formula,
R ¹ is hydrogen, halogen, cyano, C _1-8 alkyl or halogen substituted C _1-8 alkyl; n is 1, 2 or 3, and when n is 2 or 3, R &lt; ¹ &gt; may be different;
R ² is hydrogen or methyl;
R &lt; ⁶ &gt; is hydrogen, di-Ci- _8alkyl or = O;
o and m are independently of each other 0, 1 or 2;
R ⁴ is C _1-8 alkyl, substituted by a C _1-8 alkyl, hydroxy C _1-8 alkyl substituted with halogen, C _1-8 alkyl, optionally substituted with C _3-7 cycloalkyl, (CH _{2) 2 , 3-} OC _1-8 alkyl, CH (CH ₃ ) CH ₂ -OC _1-8 alkyl, (CH ₂ ) _q CN, bicyclo [2.2.1] heptanyl, or
Optionally substituted with C _1-8 alkyl, substituted by halogen, C _1-8 alkyl, C _1-8 alkoxy or halogen (CH _{2) q} -C _3-7 cycloalkyl, or
(CH ₂ ) _q -heterocycloalkyl, (CH ₂ ) _q -C _6-14 aryl, CH (C _1-8 alkyl) -C _6-14 aryl, CH (C _3-7 cycloalkyl) -C _{6- 14} aryl, or (CH ₂ ) _q -heteroaryl, wherein said heterocycloalkyl, C _6-14 aryl or heteroaryl ring is optionally substituted with halogen, C _1-8 alkyl, C _1-8 Alkyl, S (O) ₂ -C _1-8 alkyl, cyano or C _1-8 alkoxy;
q is 0, 1 or 2;
Wherein said heterocycloalkyl comprises at least one heteroatom selected from N, O and S and comprises from 3 to 7 ring atoms, said heteroaryl comprising at least one heteroatom selected from N, O and S and having from 5 to 14 Ring atoms. 15. The method of claim 14,
The compound of Formula Ig [(3S, 4R) -4- (4- chloro-phenyl) -1- (1,1-dioxo-hexahydro--1λ ^{6-thiopyran-4-carbonyl)} -pyrrolidin Pyridin-3-yl] -methyl-carbamic acid 4-fluoro-phenyl ester. A process for the preparation of a compound of formula (I) as defined in claim 1,
a) coupling a compound of formula (II) with a carbamoyl chloride, an acid chloride or a carboxylic acid to obtain a compound of formula (I); or
b) coupling a compound of formula (III): with a mixture of chloroformate, acid anhydride, or triphosgene and an alcohol to obtain a compound of formula
&Lt; / RTI &gt;
(I)

&Lt; RTI ID = 0.0 &

(III)

In this formula,
The substituents R ¹ , R ² , R ³ , R ⁴ and n are as defined in claim 1. 16. The method according to any one of claims 1 to 15,
16. A compound according to claim 16 prepared by the process according to claim 16. delete 15. A method of treating depression, pain, psychosis, Parkinson's disease, schizophrenia, anxiety or attention deficit hyperactivity disorder (ADHD), comprising administering to a patient in need thereof an effective amount of a compound according to any one of claims 1 to 15 and a pharmaceutically acceptable excipient. Medicines for treatment. delete delete delete 15. A method of treating depression, pain, psychosis, Parkinson's disease, schizophrenia, anxiety or attention deficit hyperactivity disorder (ADHD), including administration of an effective amount of a compound as defined in any of claims 1 to 15 to an animal other than a human. ). 17. The method of claim 16,
Wherein said step a) or b) further comprises the step of converting the compound obtained into a pharmaceutically acceptable acid addition salt.